ALTERATIONS IN COGNITIVE SYSTEMS, CEREBRAL HEMODYNAMICS, AND MOTOR FUNCTION

Types of Seizures

Seizures are classified in different ways—by clinical manifestations, site of origin, EEG correlates, or response to therapy.¹⁷ A simplified version of the international classification of epileptic seizures is presented in Table 16-9. Generalized seizures, 30% of seizures, involve neurons bilaterally, often do not have a local (focal) onset, and usually originate from a subcortical or deeper brain focus. Generalized seizures result from cellular, biochemical, or structural abnormalities of a widespread nature.¹⁶ With a generalized seizure, consciousness always is impaired or lost. Partial seizures (focal seizures) involve neurons only unilaterally, often have a local (focal) onset, and originate from discrete areas usually associated with structural abnormalities localized to the cortical brain tissue, thereby having a superficial focus. Consciousness may be maintained as long as the seizure activity is limited to one hemisphere in simple partial seizures, but partial seizures may become generalized to involve neurons of the other hemisphere and the deeper brain nuclei. This process is called secondary generalization. Consciousness is lost at the point of generalization. In complex partial seizures, consciousness is impaired; that is, the person is unable to respond normally to exogenous stimuli. Sixty percent of seizures are either complex partial seizures or seizures with secondary generalization.

Status epilepticus in adults is a state of continuous seizures lasting more than 5 minutes or rapidly recurring seizures before the person has fully regained consciousness from the preceding seizure or a single seizure lasting more than 30 minutes.¹⁸ The person is still in a postictal state (state that follows a seizure) when the next seizure begins. Status epilepticus most often results from abrupt discontinuation of antiseizure medications but also may occur in untreated or inadequately treated persons with seizure disorders. The situation is a medical emergency because of the resulting cerebral hypoxia. Mental retardation, dementia, other brain damage, and even death are serious threats. Aspiration also is a great risk. (Terminology associated with seizure activity is defined in Table 16-10.)

Diseases and Conditions Associated with Seizure Disorders

Any condition that changes the neuronal environment may produce seizure activity, so in theory, anyone can have a seizure. Diseases or other processes that involve the nervous system may cause a seizure disorder. The onset of seizures may point to the presence of an ongoing primary neurologic disease. Etiologic factors in seizures include (1) cerebral lesions, (2) biochemical disorders, (3) cerebral trauma, and (4) epilepsy. Conditions that may produce a seizure are metabolic defects, congenital malformations, genetic predisposition, perinatal injury, postnatal trauma, myoclonic syndromes, infection, brain tumor, vascular disease, fever, and drug or alcohol abuse or both.

Seizures also may be precipitated by hypoglycemia, fatigue or lack of sleep, emotional or physical stress, febrile illness, large amount of water ingestion, constipation, use of stimulant drugs, withdrawal from depressant drugs (including alcohol), hyperventilation (respiratory alkalosis), and some environmental stimuli, such as blinking lights, a poorly adjusted television screen, loud noises, certain odors, or merely being startled. Women immediately before or during menses may have increased seizure activity.

PATHOPHYSIOLOGY

Basic Pathologic Mechanisms

Seizures occur when there is disruption in the balance of excitation and inhibition.¹⁹ The primary abnormality may be a membrane defect leading to instability in resting potential, abnormalities of potassium conductance or calcium channels, defects of the gamma-aminobutyric acid (GABA) inhibitory system, or an abnormality in excitatory transmission enhancement, particularly of the N-methyl-D-aspartate type. In animal models, a defect in the GABA inhibitory system is the mechanism causing generalized seizures. Three groups of physiologic mechanisms are involved in seizures and epilepsies: (1) mechanisms of seizure initiation and propagation (excitation and inhibition), (2) mechanisms of epileptogenesis, and (3) genetics.¹⁹

Seizure initiation is characterized by two simultaneous events in a group of neurons: (1) high-frequency bursts of action potentials and (2) hypersynchronization. The burst activity is produced by a relatively long-lasting depolarization of the neuron caused by an influx of extracellular calcium that opens the voltage-dependent sodium channel. The influx of sodium generates repetitive action potentials.¹⁶ The firing of involved neurons becomes increasingly greater in frequency and amplitude. With sufficient neuronal activation, recruitment of surrounding neurons occurs through a variety of mechanisms. The discharge spreads or propagates to adjacent normal neurons through corticocortical synapses. If uninhibited at this point, the cortical excitation spreads through interhemispheric tracts to the contralateral cortex and through projection pathways to the subcortical areas of the basal ganglia, thalamus, and brainstem. The excitation spread to the subcortical, thalamic, and brainstem areas corresponds to the tonic phase (phase of muscle contraction with increased muscle tone) and is associated with loss of consciousness. Autonomic clinical manifestations also may emerge at this point, and apnea may be present for a few seconds. The excitation is further projected downward to the spinal cord neurons through the corticospinal and reticulospinal pathways.

The clonic phase (phase of alternating contraction and relaxation of muscles) begins as inhibitory neurons in the cortex, anterior thalamus, and basal ganglia begin to inhibit the cortical excitation. This inhibition causes an interruption in the seizure discharge, producing an intermittent contract-relax pattern of muscle contractions. The intermittent clonic bursts gradually become more and more infrequent until they finally cease. At this point the epileptogenic neurons are exhausted and the neuronal membranes probably are hyperpolarized.

The maintenance of seizure activity demands a 250% increase in adenosine triphosphate (ATP). Cerebral oxygen consumption is increased by 60%. Although cerebral blood flow also increases approximately 250% during seizure activity, available glucose and oxygen are readily depleted. With a severe seizure the brain tissue may require more ATP than can be produced by the tissues from the available oxygen and glucose. A deficiency of ATP, phosphocreatine, and glucose then occurs, and lactate accumulates in the brain tissues. Severe seizures thus may produce secondary hypoxia, acidosis, and lactate accumulation, all of which are imbalances that may result in progressive brain tissue injury and destruction. Cellular exhaustion and destruction are consequences of these events.

Epileptogenesis refers to the transformation of a normal neuronal network into one that is chronically hyperexcitable (epileptogenic focus).²⁰ A delay of months to years often occurs between the initiating injury and the first seizure. Some forms of epileptogenesis involve structural changes in the neuronal network. Reorganization or “sprouting” of surviving neurons also has been found to affect the excitability of the network.

If a seizure focus is active for a prolonged period, a secondary focus, called a mirror focus, may develop in normal tissue. This process apparently is caused by the interhemispheric communication, inasmuch as the mirror focus is located in the contralateral cortical area. Seizure threshold in some individuals is genetically lower. Research is in progress to identify alterations in gene transcription that affect seizure threshold.²¹

Agnosia

Agnosia is a defect of pattern recognition—a failure to recognize the form and nature of objects. The disorder involves the loss of recognition through one sense, although the object or person may still be recognized by other senses. Agnosia can be tactile, visual, or auditory. For example, an individual may be unable to identify a safety pin by touching it with a hand but be able to name it when looking at it. Agnosia may be as minimal as a finger agnosia (failure to identify by name the fingers of one’s hand) or more extensive, such as a color agnosia.

Agnosia is produced by dysfunction in the primary sensory area or in the interpretive areas of the cerebral cortex (see Figure 16-9). (The types of agnosia and the associated area that is most commonly involved with each are presented in Table 16-14.) Although agnosia most commonly is associated with cerebrovascular accidents, it may arise from any pathologic process that injures these specific areas of the brain.

Dysphasia

Dysphasia is impairment of comprehension or production of language (semantic processing). With dysphasia, comprehension or use of symbols, in either written or verbal language, is disturbed or lost. Aphasia is loss of the comprehension or production of language.

Dysphasias usually are associated with cerebrovascular accidents involving the middle cerebral artery or one of its many branches. The language disorders, however, may arise from a variety of injuries and diseases—vascular, neoplastic, traumatic, degenerative, metabolic, or infectious. Dysphasia results from dysfunction in the left cerebral hemisphere, most commonly in the frontotemporal region, particularly around the insula (see Figures 14-7 and 14-9). Genes located on several chromosomes have been linked to language development and disorders.^35,36 Most language disorders are caused by acute processes that either resolve or cause a chronic residual deficit. Some language disorders are caused by degenerative disorders that make the dysfunction progressive.

Dysphasias have been classified anatomically and functionally. Other classifications are linguistic and describe fluency, volume, or quantity of speech. Pure forms of any language dysfunction, however, are rare. Expressive dysphasias are characterized primarily by expressive deficits, but a verbal comprehension (auditory-receptive element) deficit may be present. Receptive dysphasias may have expressive deficits. (Table 16-15 compares types of dysphasias; Table 16-16 illustrates some of the language disturbances.)

Dysphasias, referred to as transcortical dysphasias (transcortical sensory dysphasia, mixed transcortical dysphasia, isolated speech center), involve the ability to repeat (called echolalia) and recite. Speech is fluent but with striking paraphrases. The individual cannot read and write, and comprehension is impaired.

Transcortical dysphasias are caused by hypoxia from prolonged hypotension, carbon monoxide poisoning, or other mechanisms that destroy the border zone (watershed area) of the anterior, middle, and posterior cerebral arteries (see Figure 14-19). Blood supply is marginal in this region. Hypoxia in this area occasionally may isolate the posterior speech areas or all the speech areas from the remainder of the cortex, although both areas remain intact. The sensory and motor speech areas therefore are functional, but connections with other sensory or motor areas are impaired. Information from the remaining areas of the cortex cannot be transmitted to the Wernicke area to be transformed into language.

Acute Confusional States

Acute confusional states (acute cerebral failure or acute brain failure) is an acquired mental disorder characterized by deficits in attention and coherence of thoughts and actions often associated with an altered level of arousal, global cognitive dysfunction, perceptual disturbances, sleep-wake cycle disruption, affective disturbance, and emotional liability.³⁷ Acute confusional states result from dysfunction secondary to such causes as drug intoxication, metabolic disorders, or nervous system disease. A common cause of an acute confusional state is withdrawal from alcohol, barbiturate, or other sedative drug ingestion. Acute confusional states of toxic origin may have either sudden or gradual onset, depending on the amount of exposure to the toxin. These states often occur with febrile illnesses, with systemic diseases such as heart failure, after head injury or anesthesia, postnatally, or with certain focal cerebral lesions.³⁸

PATHOPHYSIOLOGY Acute confusional states arise from disruption of a widely distributed neural network involving the reticular activating system of the upper brainstem and its projections to the thalamus, basal ganglion, and specific association areas of the cortex and limbic areas. Delirium (hyperkinetic confusional states) is associated with right middle temporal gyrus or left temporo-occipital junction disruption.³⁷ These areas receive extensive input from the limbic areas and modulate motivational and affective aspects of attention. Hypokinetic confusional states are more likely associated with right-sided frontal-basal ganglion disruption.³⁷ These areas modulate motor exploratory aspects of attention.

Most metabolic disturbances that produce a confusional state interfere with neuronal metabolism or synaptic transmission. Many drugs and toxins also interfere with neurotransmission function at the synapse. Cholinergic pathways critical for attention and arousal are often disrupted.

CLINICAL MANIFESTATIONS The predominant features of an acute confusional state are impaired or lost detection. Because of dysfunction of the anterior cingulate gyrus (see Figures 16-10 and 14-7), the ability to focus, sustain, or shift attentional focus is seriously impaired or completely lost. The person is highly distractible and unable to concentrate on incoming sensory information or on any particular mental or motor task. Besides impaired attention, the person loses coherence of thought and actions. The person may persist in thoughts or actions that are no longer appropriate (perseveration) and be unable to monitor the environment for events of importance (impaired vigilance). The person demonstrates irrelevant or inappropriate responses.

The onset of an acute confusional state usually is abrupt rather than insidious. The first clinical manifestations are difficulty in concentration, restlessness, irritability, tremulousness, insomnia, and poor appetite. Later there are top-down processing problems, including misperception, illusion, hallucination, and delirium. Obsessions, compulsive behavior, and rituals may be evident.

In hypokinetic acute confusional states, the individual exhibits decreases in mental function. Alertness is decreased, as are attention span, accurate perception, and interpretation of the environment. Forgetfulness is prominent. Reactions to the environment are slowed and indecisive. The individual dozes frequently.

Delirium, an acute hyperkinetic confusional state, typically develops over 2 to 3 days. Early clinical manifestations include difficulty in concentrating, restlessness, irritability, insomnia, tremulousness, and poor appetite. Some persons experience seizures. Unpleasant, even terrifying, dreams may occur.

In a fully developed delirium state, the individual is completely inattentive and perceptions are grossly altered. Misperception and misinterpretation are predominant. Hallucinations may be present. The person appears distressed and often very perplexed. Conversation is incoherent. Frank tremor is evident, and a great deal of restless movement is common. Violent behavior may be present. The individual cannot sleep, is flushed, and has dilated pupils, a rapid pulse (tachycardia), temperature elevation, and perfuse sweating (diaphoresis). Delirium typically abates suddenly or gradually in 2 to 3 days, although occasional delirium states persist for several weeks.

EVALUATION AND TREATMENT An acute confusional state is an acute medical problem. The initial goal is to establish that the individual is confused, and the cause must be distinguished as organic or functional (Table 16-17). Next the goal is to determine whether the confusion is delirium, an acute hypokinetic confusional state, or an underlying dementia. The precise cause of an acute confusional state is established through the complete history and physical examination. Laboratory tests include an electrocardiogram and blood, urine, CSF, and radiologic studies.

Once the cause is established, treatment is directed at controlling the primary disorder. In an acute confusional state, all drugs that may be contributing to or causing the condition are discontinued unless the problem is the result of drug withdrawal. Supportive measures are designed to enhance coping skills and to minimize the individual’s need for altered cortical functions. Supportive and protective management also involves maintaining the person’s intact cortical functions by promoting use of these functions. Agitated behavior is managed with neuroleptic medication.

Dementing Processes

Dementia is a syndrome that may be caused by a number of different illnesses. Dementia is the progressive failure (an acquired deterioration) of many cerebral functions that is not caused by an impaired level of consciousness.^39,40 Memory is the most common cognitive ability lost⁴¹ but the dementias are all characterized by reduction in cognitive functions (intellectual function). Mental abilities are impaired, with a decrease in orienting, recent memory, remote memory, language, executive attentional functions, and alterations in behavior (Box 16-2). The greatest risk factor is age.⁴¹

Dementias can be classified according to etiologic factors (e.g., trauma, tumors, vascular disorders, infections) and to associated clinical and laboratory signs. Dementing processes have been grouped as cortical, subcortical, or both. Box 16-3 lists the most and least common causes of dementia. Alzheimer disease (AD) is the most common cause followed by vascular disease, then dementia associated with Parkinson disease.⁴¹ In people younger than 60 years, frontotemporal dementia (FTD) rivals AD in terms of frequency.⁴¹ Disruption in cerebral neural circuits is present. The culmination of a progressive dementing process is nerve cell degeneration and brain atrophy involving the cerebral cortex, diencephalon, and basal ganglia.

PATHOPHYSIOLOGY Mechanisms in dementing processes include (1) degeneration possibly caused by genetics, inflammation, or biochemical alterations; (2) atherosclerosis, multiple foci of infarction throughout the thalami, basal ganglia, cerebral projection pathways, and associated areas; (3) trauma, lesions in the cerebral convolutions, mainly frontal and temporal, corpus callosum, and mesencephalon; and (4) compression, increased intracranial pressure, and chronic hydrocephalus.

The major degenerative dementias are AD, FTD, dementia with Lewy bodies (DLB), Huntington disease (HD), and prion disorders including Creutzfeldt-Jakob disease (CJD). The molecular basis for these dementias is contrasted in Table 16-18. In some instances a familial history of dementia increases by four times the likelihood that dementia will develop. Environmental influences also may play a role in the pathogenesis of dementia. The exact nature of the influence of environmental factors, such as aluminum, is not clearly understood as yet.

CLINICAL MANIFESTATIONS A summary of the clinical manifestations of the degenerative dementias is presented in Table 16-19.

EVALUATION AND TREATMENT Establishing the cause for a dementing process may be complicated, but anyone evidencing the clinical manifestations of dementia should be evaluated with laboratory and neuropsychologic testing to identify underlying conditions that may be treatable.

If a specific treatable cause is identified, the appropriate treatment is initiated. For example, an infectious process requires the appropriate antibiotic, and a potentially resectable mass may require neurosurgery. Nutritional deficiencies are corrected. If the cause is metabolic, the imbalance is corrected or the metabolic disorder is treated, or both.

Unfortunately no specific treatment or cure exists for most progressive dementias. In such instances, therapy is directed at maintaining and maximizing the remaining capacities, restoring functions if possible, accommodating to lost abilities, and controlling behavioral changes. Delusions, paranoia, and hallucinations often respond to neuroleptic medications. If coexisting depression is suspected, a trial of antidepressants is appropriate. Assisting the family to understand the dementing process and to learn ways to assist the demented individual is an essential component of supportive management.

Alzheimer Disease

Alzheimer disease (dementia of Alzheimer type [DAT], senile disease complex) is a common neurologic disorder. Formerly believed to occur mostly in people younger than 65 years (familial, early onset dementia), AD has been demonstrated to be one of the most common causes of severe cognitive dysfunction in older adults. Its more prevalent forms are late-onset familial Alzheimer dementia (FAD) and nonhereditary, or sporadic, late-onset AD (70% of cases). FAD and sporadic, late-onset AD are known as senile dementia of the Alzheimer type (SDAT). AD is also associated with Down syndrome. It is estimated that 5 million Americans have AD.⁴²

Early-onset FAD includes at least three gene defects: amyloid precursor protein (APP) gene on chromosome 21, presenilin 1 (PSEN1) on chromosome 14, and PSEN2 on chromosome 1.^43,44 Late-onset FAD is linked to a defect in the apolipoprotein E (apoE4) gene on chromosome 19.⁴⁵ Presence of the apoE4 allele is a marker of increased susceptibility rather than a genetic determinant.⁴⁰ The 3% of those who are homozygous for apoE4 have an 85% risk, whereas the 25% who are heterozygous have a 45% to 50% risk.⁴⁰ The greatest risk factors are age and familial disposition (family history).^40,41,46

Other risk factors include atherosclerosis, low education level, head injury, cardiovascular diseases, elevated serum homocysteine and cholesterol levels, and female gender estrogen deficit (Figure 16-12).⁴⁷ Protective factors include lifelong activity, apoE2, antioxidant substances, estrogen replacement, low caloric diet, nonsteroidal anti-inflammatory agents, and statins.⁴⁷

PATHOPHYSIOLOGY The exact cause of AD is unknown. Several possible theories being investigated include loss of neurotransmitter stimulation by choline acetyltransferase; mutation for encoding amyloid precursor protein; alteration in apoE, which binds amyloid-beta⁴⁸; and pathologic activation of N-methyl-D-aspartate (NMDA) receptors resulting in an influx of excess calcium.

The pathogenesis of AD is linked to amyloid-beta (AB) peptide. AB peptide is derived from proteolysis of APP and released as AB 30 to AB 46, with AB 40 and AB 42 the most abundant isoforms produced.⁴⁷ These peptides have a strong tendency to form clusters of fibrils, especially AB 42.⁴⁷ A balance between production and catabolism (involving microglia, macrophages, and bulk flow across the blood-brain-barrier) is required.⁴⁷ Altered production and failure of clearance of amyloid from the brain occur in AD initiating accumulation (Figure 16-13). Fine diffuse plaques (senile plaques) are the initial accumulation of AB 42. This accumulation is followed by other AB depositions along with tau protein, activated glia, and, eventually, neurofibrillary tangles.⁴⁷ The abnormal AB is neurotoxic.

Microscopically the tau protein that normally stabilizes the microtubular transport system in the neurons detaches from the microtubule and forms insoluble helical filaments⁴⁰ called neurofibrillary tangles (see Figure 16-13). Tangles are flame shaped. Cortical nerve cell processes become twisted and dilated because of accumulation of the same filaments that form tangles. Amyloid also is deposited in cerebral arteries, causing an amyloid angiopathy. Senile plaques and neurofibrillary tangles are more concentrated in the cerebral cortex and hippocampus. The greater the number of senile plaques and neurofibrillary tangles, the more dysfunction associated with AD. Figure 16-14 shows the disturbance in blood flow in AD. In addition, aging and injury may result in changes that contribute to the development of this disease. Such changes could include decreased oxygen and glucose transport, loss of the blood-brain barrier, and mitochondrial defects that alter cell metabolism and processing of proteins, including amyloid (apoE4). Macroscopically, the brain in AD decreases in volume and weight, the sulci widen, and the gyri thin, especially in the temporal and frontal lobes. The ventricles enlarge to fill the space (Figure 16-15).

CLINICAL MANIFESTATIONS Initial clinical manifestations are subtle and nonspecific and often attributed to forgetfulness, emotional upset, or other illness. The individual becomes progressively more forgetful over time, particularly in relation to recent events. Memory loss increases as the disorder advances, and the person becomes disoriented and confused. The ability to concentrate declines. Abstraction, problem solving, and judgment gradually deteriorate. A failure in mathematic calculation ability, language, and visuospatial orientation occurs. Dyspraxia may appear. The mental status changes induce behavioral changes, including irritability, agitation, and restlessness. Mood changes also result from the deterioration in cognition. The person may become anxious, depressed, hostile, emotionally labile, and prone to mood swings. Motor changes may occur if the posterior frontal lobes are involved. The individual exhibits rigidity (paratonia, gegenhalten), with flexion posturing, propulsion, and retropulsion. Great variability in age of onset, intensity and sequence of symptoms, and location and extent of brain abnormalities occurs among individuals with AD. Table 16-20 presents the clinical findings in each stage of AD.

EVALUATION AND TREATMENT The diagnosis of AD is made by ruling out other causes of a dementing process by CT and blood tests. The clinical history, cognitive testing, and the course of the illness are used for diagnosis. The course of the disorder is highly variable, usually developing over 5 years or more. Genetic tests to screen for early onset AD genes are PSEN1, PSEN2, APP, and apoE4.^49,50

There are no disease-arresting therapies available for AD. Cholinesterase inhibitors (ChE-Is) are used in mild to moderate AD to enhance cholinergic transmission. Drugs for

moderate to severe AD block the activity of glutamate and work as an uncompetitive NMDA receptor antagonist.^51,52

Treatment of AD also is directed at decreasing the need for the impaired cognitive function by a compensation technique, such as memory aids, maintaining those cognitive functions that are not impaired, and maintaining or improving the general state of hygiene, nutrition, and health. Environmental management, counseling, education, pharmacotherapy, and health promotion measures provide the foundation on which a comprehensive treatment program is built.⁵¹

Supratentorial Herniation

The three types of supratentorial herniation syndromes are (1) uncal (temporal lobe, lateral transtentorial) herniation, (2) central (transtentorial) herniation, and (3) cingulate gyrus herniation. Uncal herniation (hippocampal herniation, lateral mass herniation) occurs when the uncus or hippocampal gyrus (or both) shifts from the middle fossa through the tentorial notch into the posterior fossa, compressing the ipsilateral third cranial nerve impairing parasympathetic function carried in periphery of the nerve, then the contralateral third cranial nerve, and finally the mesencephalon-inducing coma. Uncal herniation generally is caused by an expanding mass in the lateral region of the middle fossa. The earliest signs of uncal herniation are poor concentration, drowsiness, and the bilateral corticospinal tract signs of increased tone and a positive Babinski sign caused by pressure on the opposite cerebral peduncle in some cases.^2,6 The classic manifestations of uncal herniation are a decreasing level of consciousness, pupils that become sluggish before fixing and dilating (first the ipsilateral, then the contralateral pupil), Cheyne-Stokes respirations (which later shift to central neurogenic hyperventilation), the appearance of decorticate, then later decerebrate, posturing, and ipsilateral hemiplegia because of contralateral corticospinal tract compression.⁶

Central transtentorial herniation is the straight downward shift of the diencephalons (thalamic medial structures) through the tentorial notch. Causes of central herniation are injuries or masses located around the outer perimeter of the frontal, parietal, or occipital lobes; extracerebral injuries around the central apex (top) of the cranium; bilaterally positioned injuries or masses; and unilateral cingulate gyrus herniation. The heralding signs are miotic pupils and drowsiness.² The individual experiencing transtentorial herniation rapidly passes from a conscious to an unconscious state; from Cheyne-Stokes respirations to apnea; from small, reactive pupils to dilated and fixed pupils; and from decortication to decerebration.

Cingulate gyrus herniation (subfalcine or transfalcial herniation) occurs when the cingulate gyrus shifts under the falx cerebri. Little is known about the clinical manifestations of this type of herniation except that there are signs of a mass causing increased intracranial pressure.⁶

Infratentorial (Foraminal) Herniation

Two types of infratentorial (foraminal) herniation syndromes may occur. In the most common infratentorial herniation syndrome, a cerebellar tonsil shifts through the foramen magnum because of increased pressure within the posterior fossa. The clinical manifestations of this downward infratentorial herniation are an arched, stiff neck; paresthesias in the shoulder area; decreased consciousness; respiratory abnormalities and arrest; and pulse rate variations. Occasionally the pressure force is such that an upward transtentorial herniation of a cerebellar tonsil or the lower brainstem results. No specific set of clinical manifestations is associated with this infratentorial herniation syndrome.

Types of Hydrocephalus

Obstruction within the ventricular system, called noncommunicating hydrocephalus or internal (intraventricular) hydrocephalus, may result from congenital abnormalities in the ventricular system or mass lesions such as a tumor that compresses one of the structures of the ventricular system (see Chapter 19 for additional discussion). Impaired absorption of CSF from the subarachnoid space occurs when an obstructive process disrupts the flow of CSF through the subarachnoid space. The fluid is prevented from reaching the convex portion of the cerebrum, where the arachnoid granulations are located.

Hydrocephalus from impaired absorption may be caused by adhesions from inflammation, as with a meningitis or subarachnoid hemorrhage; compression of the subarachnoid space by a mass, such as a tumor; congenital abnormalities of the subarachnoid space; or high venous pressure within the sagittal sinus. This type of hydrocephalus is termed communicating (extraventricular) hydrocephalus. The most common causes of communicating hydrocephalus are subarachnoid hemorrhage, developmental malformation, head injury, and neoplasm.

One form of communicating hydrocephalus is hydrocephalus ex vacuo, which arises from cerebral atrophy. CSF fills the unoccupied space. The amount of CSF is increased, but the fluid is not under pressure. Another form of communicating hydrocephalus is normal-pressure hydrocephalus (low-pressure, adult, or occult hydrocephalus), which occurs mostly in late middle age. The cause is thought to be arachnoid adhesions and thickening of the arachnoid that obstructs the subarachnoid space. This form of hydrocephalus is most often seen as a complication of head injury and subarachnoid hemorrhage.

Course of the Disease

Hydrocephalus may develop from infancy through adulthood. Congenital hydrocephalus (i.e., ventricular enlargement before birth) is rare. Noncommunicating hydrocephalus is more commonly seen in children. The more common type of hydrocephalus in adults is the communicating type. (Hydrocephalus in children is discussed in Chapter 19.)

Most cases of hydrocephalus develop gradually and insidiously over time. Acute hydrocephalus, however, may develop in several hours in persons who have sustained head injuries. Acute hydrocephalus contributes significantly to increased ICP.

PATHOPHYSIOLOGY The obstruction of CSF flow associated with hydrocephalus produces dilation of the ventricles proximal to the obstruction. Obstructed CSF is under pressure, causing atrophy of the cerebral cortex and degeneration of the white matter tracts. There is selective preservation of gray matter. When excess CSF fills a defect caused by atrophy, a degenerative disorder, or a surgical excision, this fluid is not under pressure; therefore, atrophy and degenerative changes are not induced.

CLINICAL MANIFESTATIONS The presentation of acute hydrocephalus is one of rapidly developing increased intracranial pressure. The person deteriorates rapidly into a deep coma if not promptly treated. Normal-pressure hydrocephalus has a long-term presentation and develops slowly over time. The individual or family of the individual complains of declining memory and cognitive function. An unsteady, broad-based gait with a history of falling is common. Additional clinical manifestations are apathy; inattentiveness; and indifference to self, family, and the environment. Urinary incontinence is present.⁵⁴

EVALUATION AND TREATMENT The diagnosis is made on the basis of physical examination, CT scan, and MRI. A radioisotopic cisternogram may be performed to aid in diagnosing normal-pressure hydrocephalus. Hydrocephalus can be treated by surgery to resect cysts, neoplasms, or hematomas or by ventricular bypass into the normal intracranial channel or into an extracranial compartment using a shunt. Excision or coagulation of the choroid plexus is needed occasionally when a papilloma is present. In normal-pressure hydrocephalus, reduction in CSF through a diuresis regimen often is used.

Hypotonia

In hypotonia (decreased muscle tone), passive movement of a muscle occurs with little or no resistance. Hypotonia is thought to be caused by decreased muscle spindle activity secondary to decreased excitability of neurons. Hypotonia is caused by pure pyramidal tract damage (a rare occurrence) and cerebellar damage. A pure pyramidal tract injury produces hypotonia and weakness. The hypotonia contributes to the ataxia and intention tremor in cerebellar damage and manifests with minimal weakness, with normal or slightly exaggerated reflexes. Hypotonia, often described as flaccidity (a state in which the muscle may be moved rapidly without resistance), occurs when nerve impulses necessary for muscle tone are lost, such as in spinal cord injury or cerebrovascular accident.

Individuals with hypotonia report that they tire easily (asthenia) or are weak, signs that can be observed during their activity attempts. They may have difficulty rising from a sitting position, sitting down without using arm support, and walking up and down stairs, as well as an inability to stand on their toes. Because of their weakness, accident proneness during locomotion and self-care activities is common. Inasmuch as the joints become hyperflexible in hypotonic states, people with hypotonia may be able to assume positions that require extreme joint mobility. The joints may appear loose, and the knee jerks are pendulous.

The muscle mass atrophies because of decreased input entering the motor unit. Muscle cells gradually are replaced by connective tissue and fat. The muscles are flabby on palpation and are flat in appearance. Fasciculations may be present in some cases.

Hypertonia

In hypertonia (increased muscle tone), passive movement of a muscle occurs with resistance. Four types of hypertonia are described: spasticity, gegenhalten (paratonia), dystonia, and rigidity.

Spasticity results from hyperexcitability of the stretch reflexes (overactivation of the alpha motor neurons) and is associated with damage to the motor, premotor, and supplementary motor areas, as well as lateral corticospinal tract damage (Figure 16-20). Spasticity is accompanied by increased deep tendon reflexes (hyperreflexia) and the spread of reflexes (clonus).

Gegenhalten (paratonia) manifests as resistance to passive movement that varies in direct proportion to the force applied and is associated with frontal lobe injury. Paratonia is not truly an increase in tone but an increase in resistance by the person. Dystonia manifests as sustained, involuntary twisting movements caused by slow muscle contraction and may be caused by a failure in appropriate reciprocal inhibition of the muscles (Figures 16-21 and 16-22). Injury to the putamen or its outflow tracts also is associated with hemidystonia.

Rigidity produced by tonic reflex activity mediated by gamma motor neurons may be continuous or intermittent. The involved muscles are firm and tense; the increase in muscle movement is even and uniform throughout the range of passive movement. Four types of rigidity are described: plastic, or lead-pipe; cogwheel; gamma; and alpha (Table 16-23).

Individuals with hypertonia may tire easily (asthenia) or be weak. Passive and active movement is equally affected, except in paratonia, in which more active than passive movement is possible. As a result of hypertonia and weakness, accident proneness during locomotion and self-care activities is common.

The muscles may atrophy because of decreased use of the muscles. However, hypertrophy occasionally may occur in some diseases. Hypertrophy results from overstimulation of muscle fibers. Overstimulation occurs when the motor unit reflex arc remains intact and functioning but is not inhibited by higher centers. The loss of inhibition and the constant state of excitation cause continual muscle contraction, resulting in enlargement of the muscle mass (Figure 16-23). The muscles are firm on palpation.

Paresis and Paralysis

Paresis (weakness) is impairment of motor function, that is, partial paralysis with incomplete loss of muscle power. Paralysis is loss of motor function, that is, inability of a muscle group to overcome gravity. Two subtypes of paresis and paralysis are described: upper motor neuron paresis and paralysis and lower motor neuron paresis and paralysis (Table 16-24).

Hyperkinesia

Hyperkinesia (excessive movement) represents the second broad category of abnormal movements. Within this category are a number of specific hyperkinesia syndromes (Table 16-26). Also included in the general category of hyperkinesias are dyskinesias, that is, abnormal involuntary movements.

Paroxysmal dyskinesias are abnormal, involuntary movements that occur as spasms. The type of dyskinesia varies depending on the specific disorder.

Tardive dyskinesia is the involuntary movement of the face, trunk, and extremities. Although the condition occurs occasionally in individuals with Parkinson disease, it usually occurs as a side effect of prolonged first- or second-generation antipsychotic drugs.⁵⁵ The antipsychotic drugs cause denervation hypersensitivity so that it mimics the effect of too much dopamine. The most common symptom of tardive dyskinesia is rapid, repetitive, stereotypic movements. Most characteristic is continual chewing with intermittent protrusions of the tongue, lip smacking, and facial grimacing. Stereotypic movements are believed to be a form of excessive dopaminergic activity.

Other movement disorders under this category are (1) complex repetitive movements, including automatism, stereotype, complex tics, compulsions, perseverations, and mannerisms; (2) positivism (excessive reactions to certain stimuli); and (3) paroxysmal excessive activity, including cataplexy and excessive startle reaction.

Huntington Disease

Huntington disease (HD), also known as chorea, is a relatively rare, hereditary-degenerative disorder diffusely involving the basal ganglia and cerebral cortex. The onset of HD is usually between 25 and 45 years of age, when the trait may already have been passed to the victim’s children. The disorder has a prevalence rate of approximately 2 to 8 per 100,000 persons and occurs in all races.⁵⁶

PATHOPHYSIOLOGY HD is inherited as an autosomal dominant trait with high penetrance. The genetic defect is on the short arm of chromosome 4. There is an abnormally long polyglutamine tract in the huntingtin protein that is toxic to neurons caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion (40 to 70 repeats instead of 9 to 34).⁵⁷ Age of onset of symptoms is related to the length of the repeat sequences and mechanisms of toxicity. Increased length leads to progressively earlier presentations.

The principal pathologic feature of HD is severe degeneration of the basal ganglia, particularly the caudate and putamen nuclei, and the frontal cerebral cortex (Figures 16-27 and 16-28). Tangles of protein collect in brain cells and chains of glutamine on the abnormal molecules stick to each other.⁵⁸ Early in the disease, selective loss of the striatal GABA/enkephalin pathway to the lateral aspect of the pallidum occurs. The basal ganglia normally contain a preponderance of GABAergic (GABA-secreting) neurons, including the pathway between the basal ganglia and substantia nigra (pallidonigral pathway). Basal ganglia and nigral depletion of GABA, an inhibitory neurotransmitter, is the principal biochemical alteration in HD. Degeneration of the GABAergic pallidonigral pathway causes GABA depletion in the substantia nigra with decreased inhibitory GABA activity on dopaminergic neurons in the substantia nigra and a relative excess of dopaminergic activity in the basal ganglial feedback circuit within the cerebral cortex. A relative excess of dopaminergic activity in this circuit, as in HD, is manifested by hypotonia and hyperkinesia (involuntary, fragmentary movements such as chorea). Loss of excitatory glutamate may liberate the pathway from the thalamus to the premotor cortex, impairing modulation of movement later in the course of the disease. Within the neurons, producing the fuel for brain activity is difficult, with a resultant buildup of lactic acid.

CLINICAL MANIFESTATIONS The classic manifestations of HD are abnormal movement and progressive dysfunction of intellectual processes (dementia) and thought processes. Any one of these features may mark the onset of the disease. Chorea is the most common type of abnormal movement affecting individuals with HD. Choreiform movements begin in the face and arms, eventually affecting the entire body. Symptoms of frontal lobe dysfunction include executive attention deficits, short-term memory loss (working memory); reduced capacity to plan, organize, and sequence, as well as bradyphrenia (slow thinking); and apathy. Restlessness, disinhibition, and irritability are common. Affectively, euphoria or depression or both may be present.

EVALUATION AND TREATMENT The diagnosis of HD is based on family history, clinical presentation of the disorder, and genetic testing. No known treatment is effective in halting the degeneration or progression of symptoms. The discovery in 1983 of the HD marker, called G8, on chromosome 4 paves the way for presymptomatic diagnosis of the disorder and isolation of the HD gene. Recombinant genetic techniques and neuroprotective drug strategies may someday prevent or control the disorder.⁵⁹

Hypokinesia

Hypokinesia (decreased movement) is loss of voluntary movement despite preserved consciousness and normal peripheral nerve and muscle function. Types of hypokinesia include akinesia, bradykinesia, and loss of associated movement.

Parkinson Disease

Parkinson disease (PD) is a commonly occurring degenerative disorder of the basal ganglia (corpus striatum, globus pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic (dopamine-secreting) nigrostriatal pathway. Nigrostriatal disorders produce a syndrome of abnormal movement called parkinsonism (Parkinson syndrome, parkinsonian syndrome).

Etiologic classification of parkinsonism includes primary parkinsonism and secondary parkinsonism (Box 16-5). The onset of PD occurs after 40 years of age, with mean onset of 60 years of age.⁶⁰ Equal incidence occurs in both sexes.²³ PD is one of the most prevalent of the primary CNS disorders and a leading cause of neurologic disability in individuals older than 60 years. Approximately 1% to 2% of the U.S. population older than the age of 60 is affected—an estimated 1.5 million individuals. The familial form represents about 10% of PD; however, the majority of cases are sporadic or idiopathic. Several PD genes have been identified, the most significant of which are identified in Table 16-18.

PATHOPHYSIOLOGY The hallmark pathologic features of PD are loss of dopaminergic pigmented neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in the putamen portion of the striatum (the striatum includes the putamen and caudate nucleus) (Figure 16-29). Dopamine loss in other brain areas including the brainstem, thalamus, and cortex also occurs.⁶¹ Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results in underactivity of the direct motor pathway (normally facilitates movement) (Figure 16-30) and overactivity of the indirect motor loop (normally inhibits movement). This results in inhibition of the motor cortex manifested with bradykinesia and rigidity. The subthalamic nucleus (STN) overactivity also influences the limbic system⁶⁰ accounting for emotional signs and symptoms. Neuronal loss within the cerebral cortex is found in one half of individuals with PD.

Lewy bodies, fibrillar intracellular eosinophilic inclusions, and high concentrations of alpha-synuclein, ubiquitin, tau protein, tuberculin, and other proteins, are found in the SN, LC, and other areas of the brain and are a marker for neuronal degeneration.⁶² Degeneration of the LC, which contains noradrenergic neurons, also occurs in PD. Norepinephrine is thought to be neuroprotective and loss of LC neurons may be associated with a worsening of disease progression and the behavioral symptoms of PD.⁶³ Molecular events thought to be associated with the neurodegeneration of PD include mitochondrial dysfunction, oxidative stress, abnormal folding and accumulation of alpha-synuclein, abnormal phosphorylation, and dysfunction of the ubiquitin proteosome system^64,65 (Figure 16-31).

CLINICAL MANIFESTATIONS Onset of symptoms is insidious and symptoms appear after a 70% to 80% loss of pigmented nigral neurons and a loss of 60% to 90% of striatal dopamine.⁶⁶ The classic motor manifestations of PD are bradykinesia, tremor at rest (resting tremor), rigidity (muscle stiffness), hypoakinesia (poverty of movement), and postural abnormalities. These manifestations may develop alone or in combination, but as the disease progresses, all four are usually present to at least some degree. There is no true paralysis. A modified Hoehn and Yahr scale⁶⁷ can be used to assess progression of symptoms:

In early stages of the disease, reflex, sensory, and mental status are usually normal. Nonmotor symptoms associated with PD include hyponosmia, fatigue, pain, autonomic dysfunction, sleep fragmentation, depression, and dementia with or without psychosis.⁶⁸

Parkinsonian tremor, the most conspicuous and most variable symptom, is usually the first motor symptom to appear. It is an asymmetric, regular, rhythmic, low-amplitude tremor (4 to 6 cycles/second, with slowly alternating flexion-extension contraction).⁶⁹ Later the tremor becomes symmetric at 7 to 12 cycles per second. It is a tremor at rest, disappearing briefly during the course of a voluntary movement and reappearing when the limb is held in a stationary position. Intensity and amplitude of the tremor vary. The arm is more affected than the leg. The head is rarely involved. Seventy percent of individuals with PD have this tremor, and 20% have a postural (kinesic) tremor or both tremor types. All tremors are increased by stress and anxiety.

Parkinsonian tremor appears to result from instability of feedback from the basal ganglia to the cerebral cortex caused by loss of the inhibitory influence of dopamine in the basal ganglia. Increased oscillation in the normal feedback cycles of the motor outflow feedback circuit when the muscles are at rest produces the tremor. When the individual performs voluntary movements, the tremor becomes temporarily blocked, presumably because other motor control signals arriving in the thalamus override the abnormal basal ganglial signals. As the disorder worsens, tremor may lessen as rigidity supervenes. The postural tremor is associated with damage to the cerebellofugal pathway to the red nucleus, a pathway that subserves communication from muscle spindles to the thalamus and motor cortex.

Parkinsonian rigidity is an increased resistance to the passive movement of a joint that impedes active and passive movement. The first symptoms of rigidity may be painful muscle cramps in the toes or hands. More commonly the limb feels stiff, heavy, tired, or aching. Plastic rigidity is constant throughout the entire range of motion and is felt as lead-pipe resistance during passive movement. Cogwheel rigidity, brief palpable jerks, is accompanied by tremor. The mechanism underlying rigidity is unclear, but there is increased resting muscle activity of antagonistic muscle groups with enhancement of the long-latency component of the stretch reflex.⁶⁰

Parkinsonian bradykinesia is poverty of associated and voluntary movements. It is the most prevalent and crippling symptom and often is overlooked in the early stages. The pathophysiology underlying the bradykinesia is an overactive subthalamic nucleus (STN) that inhibits the motor thalamus and motor cortex.⁶⁰ It is associated with dopamine deficiency and failure of the mechanism programming movement patterns manifested as a defect in the voluntary production of smooth motions at different speeds.⁷⁰

All striated muscles—extremity, trunk, ocular, facial—are affected eventually, including muscles of mastication (chewing), deglutition (swallowing), and articulation. Micrographia is present. Extreme underactivity in the individual with PD makes the person appear stiff, even when resistance to passive movement cannot be felt. Bradykinesia is a separate phenomenon from rigidity and may be severe even in the presence of rigidity. Individuals state that they feel “wooden” (as though moving against resistance) and complain of rapid, severe fatigue.

Hypokinesia, or decreased frequency or absence of associated movements, is one of the earliest akinetic symptoms. Individuals with PD sit and lie motionless for long periods without the little shifts a normal person makes to prevent discomfort and stiffness. Bradykinesia, or slowness of voluntary movements, is characterized by difficulty initiating, continuing, or synchronizing movements. Both associated and voluntary movements are interspersed by freezing (an inability to continue movement). Freezing may be precipitated by (1) increasing the effort to move, (2) turning, and (3) initiating certain types of tactile and visual contact.

Disorders of Posture (Stance)

An inequality of tone in muscle groups because of a loss of normal postural reflexes results in a posturing of limbs. Many reflex systems govern tone and posture, but the most important factor in posture control is the stretch reflex, in which stretching of extensor (antigravity) muscles causes increased extensor tone and inhibited flexor tone. Four types of disorders of posture are described: (1) dystonic posture, (2) decerebrate posture, (3) basal ganglion posture, and (4) senile posture. Equilibrium and balance are disrupted when postural disorders are present.

Dystonia is the maintenance of an abnormal posture through muscular contractions. When muscular contractions are sustained for several seconds, they are called dystonic movements, such as in choreoathetoid movements associated with high levels of L-dopa; when contractions last for longer periods, they are called dystonic postures, such as in torticollis. Dystonic postures may last for weeks, causing permanent fixed contractures. Dystonia has been associated with basal ganglia abnormality, but the exact pathophysiologic mechanisms are unknown (Box 16-6). One particularly relevant dystonic posture already discussed in this chapter is decorticate (striatal posture or upper motor neuron dysfunction posture), which may be unilateral or bilateral in occurrence. Decorticate posture (also referred to as antigravity posture or hemiplegic posture) is characterized by upper extremities flexed at the elbows and held close to the body and by lower extremities that are externally rotated and extended. Decorticate posture is believed to occur when the brainstem, which facilitates the antigravity position, is not inhibited by the motor function of the cerebral cortex. Upper motor neuron posture is more commonly described as the arm flexed at the elbow, with a wristdrop; the leg inadequately bent at the knee, with the hip excessively circumabducted; and the presence of a footdrop.

Decerebrate posture refers to increased tone in extensor muscles and trunk muscles, with active tonic neck reflexes. When the head is in a neutral position, all four limbs are rigidly extended. The decerebrate posture is caused by severe injury to the brain and brainstem, resulting in overstimulation of the postural righting and vestibular reflexes.

Basal ganglion posture refers to a stooped, hyperflexed posture with a narrow-based, short-stepped gait. This posture abnormality results from the loss of normal postural reflexes and not from defects in proprioceptive, labyrinthine, or visual function. Dysfunctional equilibrium results from the loss of postural stability, and thus the individual is unable to make the appropriate postural adjustment to tilting or loss of balance and falls instead. Dysfunctional righting is the inability to right oneself when changing from a lying or crouching to a standing position or when rolling from the supine to the lateral or prone position. Dysfunctional postural fixation is the involuntary flexion of the head and neck, causing the person difficulty in maintaining an upright trunk position while standing or walking. Basal ganglion dysfunction accounts for this posture.

Senile posture is characterized by an increasingly flexed posture similar to that caused by basal ganglion dysfunction. The posture is associated with frontal lobe dysfunction, but the primary pathophysiology is not well described.

Disorders of Gait

Four predominant types of gait disorder are (1) upper motor neuron dysfunction gait, (2) cerebellar (ataxic) gait, (3) basal ganglion gait, and (4) senile (frontal lobe, pseudoparkinsonian) gait. As with posture, equilibrium and balance are affected with gait disturbances.

Several upper motor neuron gaits exist. In the presence of mild upper motor neuron dysfunction, a footdrop may appear only with fatigue. The individual may complain of hip and leg pain. A spastic gait, which is associated with unilateral injury, is manifested by a shuffling gait with the leg extended and held stiff, causing a scraping over the floor surface. An impaired leg swing around the body rather than an appropriate lifting and placing of the leg is noted. The foot may drag on the ground, and the person tends to fall to the affected side. A scissors gait is associated with bilateral injury and spasticity. The legs are abducted, causing them to touch each other. As the person walks, the legs are still swung around the body but then cross in front of each other because of adduction. Injury to the pyramidal system accounts for these gaits.

A cerebellar gait manifests as a wide-based gait with the feet apart and often turned outward or inward for greater stability. The pelvis is held stiff, and it seems to be independent of the trunk. The individual staggers when walking. Cerebellar dysfunction accounts for this particular gait.

A basal ganglion gait and a senile gait are both broad-based gaits. The person walks with small steps and a decreased arm swing. The head and body are flexed and the arms are semiflexed and abducted, whereas the legs are flexed and rigid in more advanced states. Basal ganglion and frontal lobe dysfunction, respectively, account for these two gaits.

Disorders of Expression

Disorders of expression involve the motor aspects of communication and include (1) hypermimesis, (2) hypomimesis, and (3) dyspraxias and apraxias. Hypermimesis is a disinhibition phenomenon that most commonly manifests as pathologic laughter or crying. Pathologic laughter is associated with right hemisphere injury, and pathologic crying is associated with left hemisphere injury. The exact pathophysiology is not known. Hypomimesis manifests as aprosody, or the loss of voice modulation (pitch, speed, emphasis, emotion). Receptive aprosody involves an inability to understand emotion in speech and facial expression, whereas expressive aprosody involves the inability to express emotion in speech and facial expression. Aprosody is associated with right hemisphere damage.

Dyspraxia is the partial inability and apraxia is the complete inability to perform purposeful or skilled motor acts in the absence of paralysis, sensory loss, abnormal posture and tone, abnormal involuntary movement, incoordination, or inattentiveness. These are disorders of learned skilled movements.⁸³ Dyspraxia and apraxia are associated with vascular disorders, trauma, tumor, degenerative disorders, infections, and metabolic disorders. The medial premotor cortex, including the supplementary motor area (SMA), appears to play a role in skilled movements as does the convexity premotor areas⁸³ (Table 16-27).

True dyspraxias occur when the connecting pathways between the left and right cortical areas are interrupted causing language-motor and motor representation disconnections between the hemispheres (Figure 16-33). Dyspraxias may result from any pathologic process that disrupts the cortical areas necessary for the conceptualization and execution of a complex motor act or the communication pathways within the left hemisphere or between the hemispheres.

Basal Ganglia Motor Syndromes

Basal ganglia motor syndromes are movement disorders that involve either a paucity or an excess of movements. Stress and nervous tension typically worsen the symptoms, whereas relaxation improves motor performance. Akinesia may occur despite normal strength. Involuntary movements, such as tremor, chorea, ballism, athetosis, and dystonia, also may occur and probably are caused by the loss of the normal modulating effects of the corpus striatum and other parts of the basal ganglia.

Basal ganglia motor syndromes also are characterized by alterations in muscle tone and posture. Rigidity, together with the cogwheel phenomenon, is present in all muscle groups but is most prominent in those that maintain flexed position. Postural abnormalities result from the loss of normal postural reflexes. Dysfunctional equilibrium results from the loss of postural stability.

Cerebellar Motor Syndromes

Cerebellar motor syndromes involve the cerebellum and may result in (1) acute loss of muscle tone; (2) difficulty with coordination of voluntary movements (ataxia); (3) minor degrees of muscle weakness, tendency toward fatigue, and impairment of associated movements; and (4) disorders of equilibrium, posture, and gait. Cerebellar effects are chiefly ipsilateral (primarily affecting the same side of the body), so damage to the right cerebellum generally causes symptoms on the right side of the body. Predominant symptoms depend on the area of damage within the cerebellum. The three cerebellar syndromes are the rostral vermis, caudal vermis, and lateral syndromes⁸⁴ (Table 16-29).

Diagnosis of a cerebellar motor syndrome is based on the symptoms, but these may vary because of the individual’s attempts at compensation. Further, the nervous system often can operate well despite destruction of parts of the cerebellum, although the mechanisms responsible for this retained function are not fully understood.