323 16 Melmed S, et al. Diagnosis and treatment of hyperprolactinemia: An Endocrine Society cli nical practice guideline. J Clin Endocrinol Metabol. 2011. 96(2):273 \200\223288. Treatment of prolactin-secreting pituitary adenomas during pregnancy Increased production a nd secretion of estrogen during preg- nancy may promote growth and expansion of prolactin-s ecreting pituitary adenomas. Macroadenomas may expand and cause visual field deficits or se vere headaches. Women who require treatment of hyperprolactinemia to become pregnant should be placed on bromocriptine due to the greater certainty that it does not cause birth defec ts.If possible, dopamine agonists should be discontinued in pregnancy. Clinical monitoring every 3 months during pregnancy should include questioning about headaches and visual chang es.If the location or size of the prolactinoma requires continued medical management during pregnancy, treatment with bromocriptine can be continued or reinitiated.In cases of known macroadenomas, particu- larly those that abut the optic chiasm, expectant management may fo cus on considering surgery prior to conception to prevent potential complica- tions.Should visual acuity decline or neurologic symptoms progress during pregnancy, dedicated pituitary MRI scanning and visual field testing may be required to assess tumor growth.If necessary, surgery may be considered during the second trimester. Acromegaly A rare systemic syndrome resulting from exposure to excessive levels of GH. The most common cause is proliferation of somatotroph cells in the form of a GH-secreting pitui tary adenoma. GH stimulates increased pro- duction and secretion of IGF-1 in the liver. Ove r time, excessive circulating levels of IGF-1 may lead to growth and enlargement of somatic tissues. Signs Changes in appearance may be insidious, developing gradually over the cours e of several years (Table 9.25). Review of older photographs may help to establish timing a nd extent of changes. Overgrowth of soft tissues may lead to coarsening of facial features. Patients and observers may note bossing of the frontal bones, expansion of the nose, enlar gement of the tongue (macroglossia), deepening of the voice, and increased prominence of th e jaw with resultant spacing of the teeth. Spade-like enlargement of the hands and feet may prompt successive changes in ring and shoe sizes. Carpal tunnel syndrome, skin tag formati on, excessive sweating (hyper- hidrosis), and hirsutism are also associated with acromegaly . Bone density may be increased in men and premenopausal women. Findings consistent with le ft ventricular hypertrophy may be evident. Complications Untreated acromegaly may be associ ated with the devel- opment of hypertension, cardiomyopathy, heart failure, T2DM, hypertro- phic cardiomyopathy, colonic neoplasia, and obstructive sleep apnea. 324 Table 9.25 Evaluation of suspected acromegaly 1 Screen for elevated GH secretion by checking a serum IGF-1 level. 2 If the IGF-1 level is elevated, check a GH suppression test. \212 GH suppression test is performed by measuring a baseline GH level, administering a 75 g ora l glucose tolerance test load, then measuring GH levels at 30, 60, 90, and 120 min marks. \212 Peak GH <1 ng/mL = normal response \212 Peak GH >2 ng/mL = acromegaly 3 Consider dedicated pituitary MRI scanning with gadolinium to check for the presence of a sellar mass that may represent a GH-secreting pituitary adenoma. Note that, at the time of diagnosis, many tumors are macroadenomas (>10 mm in size). Treatment Principal treatment is surgical resection. Smaller macroad- enomas can usually be removed via transsphenoidal approaches. Removal of larger macroadenomas may require cranio tomy. Success rates following initial surgery vary. Documentation of cure may depend on dem onstrating (a) normal postsurgical IGF-1 levels, (b) postsurgical serum GH concentra- tion <2.5 ng/mL, and (c) a postsurgical GH suppression test with a peak GH <1 ng/mL. Persistent disease may require repeat surgery, treatment with external beam radiation, and/or initiati on of medical therapy targeted to inhibit secretion of GH from residual pituitary tissue or antagonize growth hormone receptors to inhibit production and secretion of IGF-1. Medical therapy targeted to inhibit secretion of GH Somatostatin analogs act by binding to somatost atin receptors on target tissues and inhibiting GH secretion. Octreotide and lanreotide are commercially available somatostatin analogs. Octreotide is available in a short-acting sub cutaneous preparation (Sandostatin ) and a long-acting IM preparation (Sandostatin LAR ). Lanreotide is only available as a long-acting analog (Somatuline Depot). Limiting side e ffects of both agents may include nausea, abdomi- nal discomfort, hyperglycemia, and cholel ithiasis. Patients who tolerate test doses may be continued on escalating doses of the shor t-acting preparation or may be switched to the long-acting preparations. Doses may be adjus ted every 6 \200\2238 wks to target normalization of IGF-1 levels. In some cases, dop- amin e agonists may also inhibit secretion of GH from residual tissue and may be used alone or i n concert with somatostatin analogs. Cabergoline (Dostinex 0.5 mg, usual starting dose 0. 25 mg twice a week) has proven to be more effective than other agents when used for this pu rpose. May be advanced as tolerated to 1 mg twice a week. Dose-limiting side effects may in clude nausea, orthostasis, and cognitive impairment. Medical therapy targeted to inhibit pr oduction and secretion of IGF-1 Pegvisomant (Somavert ) is a modified form of GH that acts by competitively binding to GH receptors, inhibiting the production and secre- tion of IGF -1 in the liver. Clinical trials have shown that it may effectively normalize IGF-1 levels in patients who have failed to respond to treatment with somatostatin analogs. Can also be used in combination with soma- tostatin analogs. Side effects of this GH receptor antagonis t include nausea, diarrhea, chest pain, and transaminitis that may require discontinuation of the drug. y g o o n i r c o d n E l 325 Diabetes insipidus Physiology of water balance Increased serum osmolality and decreased eff ective circulating volume stimulate release of antidiuretic hormone (ADH) from the supraopt ic and paraventricular nuclei in the hypothala- mus. Circulating ADH binds to receptors in the collecting tubules of the kidney, activating aquaporin channels that mediate increased reabsorption of free water (see figure). Diabetes insipidus is a disorder characterized by decreased reabsorption of free water in the collecting tubules. It may be precipitated by d isorders that (1) interrupt the release of ADH from the hypothalamus (central diabetes insi pidus) or (2) inhibit the action of ADH in the collecting tubules (nephrogenic diabetes ins ipidus). See Figure 9.2. Patients present with severe polyuria (urine output >3,000 mL/day) and compensatory polydipsia associated with the excretion of large volumes of dilute urine . Primary polydipsia Also known as psychogenic polydipsia, is caused by excessive intake of water. Commonly seen in patients with psychiatric ill- ness, although may be induced by hy pothalamic injury or infiltration affect- ing thirst center. Table 9.26 Water deprivation test 1 Starting after breakfast, hold all intake of fluids. Check the patient \200\231s baseline weight, pulse, and BP, and measure a baseline serum osmo- lality and serum sodium level. \212 \212 \212 Every hour, check the patient \200\231s weight, pulse, and BP. Every 2 h, measure a serum o smolality and serum sodium level. With each urine void, measure the urine volume and urine osmolality. 2 Consider terminating the test when one of the following endpoints has been reached* \212 \212 \212 Urine osmolality >600 mosm/kg Serum osmolality >295 \200\223300 mosm/kg* Serum sodium >145 meq/dL* 3 Interpretation: \212 Determine the maximum urine osmolality and calculate the per- centage increase in urine osm olality following administration of vasopressin, if administered. Maximum urine osmolality >500 mosm/kg = primary polydipsia Maximum urine osmolality <500 mosm/kg = central or nephro - genic diabetes insipidus Maximum urine osmolality <300 mosm/kg + 100 \200\223800% osmolal ity = complete central diabetes insipidus Maximum urine osmolality <300 mosm/kg + 15 \200 \22350% osmolality = partial central diabetes insipidus Maximum urine osmolality >300 mosm/ kg + 15 \200\22350% osmolality = partial nephrogenic diabetes insipidus Maximum urine osmol ality >300 mosm/kg + <15% osmolality = complete nephrogenic diabetes insipidus \212 \212 \212 \206\221 in urine \212 \206\221 in urine \212 \206\221 in urine \212 \206\221 in urine Administer desmopressin (10 mcg by nasal insufflation or 4 mcg SQ/IV), then measure the uri ne volume and urine osmolality with the next urine void before allowing resumption of fluid intake. 326 Causes of central diabetes insipidus Include neurosurgery, head trauma, growth of suprasell ar masses, histiocytosis, neurosarcoidosis, hypothalamic metastases, hypoxic or ischemic ev ents, and idiopathic etiologies. Causes of nephrogenic diabetes insipidus Include exposure to lithium, hypercalcemia, hypokalemia, and hereditary forms of nephrogenic diabetes insipi dus. Evaluation of polyuria Principal goal is to determine whether elevated urine output is primarily driven by increased intake of free water (pri- mary polydipsia) or by decreased reabsorption of free water (central or nephrogenic diabetes insipidus). Performance of a wa ter deprivation test (Table 9.26) may clarify this distinction while providing clues to the root cause of diabetes insipidus. Treatment of central diabetes insipidus Identify and tre at any revers- ible conditions that may be interrupting the release of ADH from the hypotha lamus. Persistent central diabetes insipidus may require long-term treatment with desmopres sin (DDAVP ), an ADH analog that has minimal vasopressor activity. Desmopressin is availab le as a 10 mcg metered nasal spray and in 0.1 mg tablet form. The usual starting dose is on e spray (10 mcg) intranasally or 0.05 mg PO taken at bedtime. Doses may be increased increm entally with expansion to twice daily administration to attenuate nocturia and daytime poly uria. Patients should be encouraged to pay atten- tion to and honor their thirst. y g o o n i r c o d n E Figure 9.2 Nephrogenic action of ADH l Treatment of nephrogenic diabetes insipidus Identify and treat any reversible conditions th at may be inhibiting the action of ADH in the col- lecting tubules. Persistent nephrogenic diabetes insipidus may respond to treatment with hydrochlorothiazide (12.5 \200\22325 mg bi d), amiloride (Midamor 5 \200\22320 mg/d), or NSAIDs. Amiloride may be particularly effec tive in attenuat- ing polyuria in patients who develop nephrogenic diabetes insipidus assoc i- ated with exposure to lithium used to treat affective disorders. 327 Neurology Jason Rosenberg , M.D. y g o o r u e l Contents Approach to the neurology patient 329 Higher functions of the cortex 333 Deep nuclei: Basal ganglia, thalamus, hypothalamus 335 Brainstem 335 Cerebellum 335 Spinal cord anatomy 336 C erebral artery territories 336 Peripheral nerves, myotomes, and dermatomes 339 N 0 1 Common chief complaints Headache 345 Migraine 349 Altered mental status 353 Dizziness 355 Deafness 357 Tinnitus 357 Abnormal movements 358 Specific diseases and conditions Ischemic stroke 359 Transient ischemic attack 363 Intracerebral hemorrhage 364 Subarachnoid hemorrhage 364 Intracranial venous thrombosis 367 Subdural hematoma 369 Epidural hematoma 369 Meningitis 370 Encephalitis 372 Multiple sclerosis 372 Transverse myelitis 376 Neuromye litis optica (Devic \200\231s) 376 328 Dementia 376 Alzheimer \200\231s disease 377 Epilepsy 378 Epilepsy: Management 380 Status epilepticus 382 Parkinson \200\231s disease and parkinsonis m 382 Tremor 384 Neuromuscular disease 384 Mononeuropathies 385 Polyneuropathies 387 Bell \200\231s palsy 38 9 Neuromuscular junction disorders 390 Lambert-Eaton myasthenic syndrome 391 Myopathies 391 Myelopathies 392 Space-occupying lesions in the brain 393 Neuroradiology 394 Approach to the neurology patient Localization For many neurological conditions, diagnosis begins with localization. In other words, to determine what type of pathology a patient is suffering, it is often helpful to start with determining where within the nervous system th e lesion lies. For example, a patient complaining of weakness might have psychogenic, corti cal, cerebellar, myelopathic (spinal cord), neuropathic, neuromuscular junction, or myopath ic pathology. Identifying the level of dysfunction within the central or peripheral nervous system is critical for developing an appropriate differential. Diseases that affect the br ain and spi- nal cord (the central nervous system) are distinct from peripheral nervous sys tem pathologies. Ironically, the proliferation of high-quality imaging techniques has made the traditional approach to the neurological history and examination more important than ev er, both in terms of avoiding unnecessary expense and in preventing futile pursuits down bl ind alleys, chasing after coincidental or spurious findings. Thus, not only is localization critical in implicating a specific disease process or pathology, but localization prior to definitive diagnosis will guide appropriate testing; i.e., whether to order a magnetic res onance imaging (MRI) of the brain, of the cervical spine, of the thoracic spine, of the lum bar spine, or whether to order an electromyographic nerve conduction study (EMG-NCS). Thus, this chapter opens with the classical neurological approach to the chief concern \200\224 localization \200\224 because it truly matters in the assessment of the individual patient. The anatomy, while admittedly dense and dry, is very much relevant. Clinically relevant ex amples will be peppered throughout to maintain your interest. Where is the lesion? Localizi ng the site of the lesion depends on recog- nizing the pattern of cognitive, cranial nerve, motor, and sensory deficits that occur following lesions at different sites within the ner vous system, as revealed by history and examination. The traditional \200\234complete \200 \235neurological exam consists of a thorough assessment of mental status and higher corti- cal function, the cranial nerves, the motor system (bulk, tone, and power), sensation (touc h, vibration, proprioception, pain, and temperature), deep tendon reflexes, coordination/ce rebellar function, and gait. Techniques of even a neurological screening examination are be yond the scope of this chapter, but for reference, a reasonably thorough documentation of a nor- mal exam is provided in Table 10.1, as are examples of abnormal findings. Weakness as sociated with aphasia or agnosia localizes the motor lesion to the cortex. Weakness associa ted with double vision or an asymmetric gag reflex signifies a brainstem lesion. Sensory lo ss below a segmental der- matome implicates spinal cord pathology. Weakness or sensory loss in the distribution of individual nerves localizes the dysfunction to the peripheral nervo us system. Patterns of motor deficits: Localizing the lesion responsible for weakness is in itially dependent on identifying whether the pattern of motor weakness is more consistent w ith lower or upper motor neuron dysfunction (LMN or UMN; see Tables 10.2 and 10.3). The upp er motor neuron is part of the central nervous system (CNS), extending all the way from the homunculus within the cortical motor strip, down through the brainstem, where they decussa te (cross the midline) in the lower brainstem medulla, travel down through the spinal cord in white matter tracts, and eventually synapse in the anterior horn of the spinal cord with the lower motor neurons, which in turn extend their axons ipsilaterally through nerve root s and peripheral nerves to specific muscles. y g o o r u e N l 329 Table 10.1 Neurological exam findings Example of a normal neurological exam, in detail Mental status: The patient is alert, atten tive, fully oriented, and appropriate in terms of behavior, mood, and affect. Historical ab ility is good. Language function is normal, with fluent speech, normal comprehension, intac t repeti- tion, and no spontaneous or confrontational word finding difficulty. There is no dysarthria. There is no agnosia, apraxia, or neglect. Fund of knowl- edge is good, and reca ll is 3/3. There is no right/left confusion, and simple coin calculations are normal. There are no frontal release signs (glabellar, palmar-mental, grasp, snout, root, paratonia). Cr anial Nerves: Olfaction is normal in each nostril (coffee). Pupils are equal, round, and re active to light and accommodation, without afferent papillary defects. Visual acuity and re d color saturation are normal in each eye. Visual fields are full to confrontation. Optic d isks are sharp with normal central venous pulsations. Extraocular movements are intact, wit h normal saccades and smooth pursuits, without nystagmus or any reported diplopia. Facial s ensation is normal to pinprick in V1, V2, and V3 distributions bilaterally. Face is symmetr ic at rest, with equal movement/normal grimace. Hearing is intact to finger rubs bilaterall y, with normal vestibular responses to head impulse testing bilaterally. Gag is intact, uvu la is midline, and palate elevates symmetrically. Head turn and shoulder shrug are 5/5 bila terally. Tongue is midline with normal movement and no atrophy or fasciculations at rest. M otor exam is normal for bulk and tone throughout, and power is 5/5 in the major proximal an d distal muscle groups of the bilateral upper and lower extremities. The patient can easily rise from a chair without the use of the arms and is able to walk on toes and on heels. Th ere is no pronator drift and no obit sign. There are no adventitious movements. Deep tendon reflexes are 2+ throughout. There are no Hoffman signs, there is no ankle clonus, and toes are downgoing (negative Babinski). Coordination is normal for fine finger movements, rapid alternating move- ments, finger-nose-finger, foot tapping, and heel-to-shin bilaterally. T here is no ataxia or dysmetria. Sensation is normal in the fingers to pinprick and texture, and in the toes to pinprick, vibration, and joint position sense. Romberg is negative. Sta tion and gait are narrow-based and normal, without limp, ataxia, imbalance, festination, ma gnetic quality, or reduced arm swing. Tandem gait is normal. (Such an exam is rarely done o r documented this exhaustively; typically a neurologist will actively \200\234tailor \200 \235 a screening exam to the individual patient and a non-neurologist will document the gro ssly abnormal findings on brief screening exam.) Example of a report of pertinent exam find ings in a patient with acute onset of new deficits: The patient is fully awake and appears frustrated but denies pain, saying a few appropriate simple words but with stammering, nonf luent, slurred speech. He is able to follow simple commands and comply with exam test- ing. The patient blinks to visual threat from both visual fields and appears to feel pinpricks equally on both sides. Eyes move conjugately but appear to be deviated to the left, and the re is obvious right facial weakness. There is a marked right-sided flaccid paresis of the a rm with reduced reflexes, with weak flexor movement of the elbow only. There is at least 4/ 5 strength of the right leg throughout, hip flexion and plantar flexion appearing to be the weakest, with slowed foot tapping. Reflexes may be slightly reduced com- pared to the left , but the right toe is upgoing. The left side is intact in terms of power, coordination, an d reflexes. The patient winces to pinprick in the arms and the legs bilaterally. Gait was n ot tested due to concerns for safety. 330 (Continued) y g o o r u e N Table 10.1 (Continued) l Or, more succinctly: The fully awake patient has a nonfluent aphasia with decent comprehens ion, left eye deviation without field cut, and left-sided flaccid hemiparesis face and arm> leg with an upgoing toe and intact sensation. Given such a report, a neurologist or other e xperienced provider would immediately suspect an acute left middle cerebral artery (MCA) te rritory stroke. Although, classically, UMN weakness is described as having increased mus- cle tone (specifi cally, spasticity) and elevated deep tendon reflexes, early in the course of CNS injuries t hese features may be absent (e.g., immediately after a stroke or spinal cord injury). Due t o the variability in UMN findings in acute CNS pathologies, it is necessary for clinicians to additionally rec- ognize colocalizing associated neurological exam findings, as well as specific muscle patterns of weakness seen with lesions affecting the brain or spinal cord. Lesions of the UMN tracts within the cortex, subcortex, internal capsule, basal ganglia, an d brainstem will cause contralateral weakness, affecting the side of the body opposite the lesion. Cortical lesions affecting neighbor- ing structures may cause additional deficits, such as aphasia (typically left hemisphere) or neglect (typically right parietal lobe). Bra instem lesions typically cause ipsilateral cranial nerve findings. Lesions within the spina l cord \200\224below the medullary decussation \200\224will cause ipsilateral UMN type weak ness (although, due to its small diameter, lesions commonly will affect both sides of the c ord and thus cause bilateral weakness). Cord lesions typi- cally affect all motor levels be low the pathology. Findings of normal arms and weak, spastic legs would imply thoracic cord pathology; affected arms and legs with normal cranial nerves and cortical function would i mplicate the cervical cord. Lesions of the lower motor neurons within the anterior horn of the spinal cord or the axons within the periphery will cause weakness with reduced muscle t one, decreased reflexes, fasciculations, and eventual atrophy. Neuromuscular junction patho logies may cause variable weakness that fluc- tuates in severity, often worse with activity ( \200\234fatigueability \200\235), the classic example being myasthenia gravis. Botulinum toxin affecting the NMJ may cause profound flaccidity. Ratings of muscle strength are give n on a 5-point scale (see Table 10.4) as determined by the examiner on direct confrontation al testing. The patient is encouraged to give maximal effort of a given muscle group, attem pting to overcome resistance provided by the examiner. Exam technique is impor- tant; the e xaminer must supply an appropriate degree of counterforce for each muscle group being teste d (e.g., fingers against fingers; arm against arm; arm and body weight against leg, with ap propriate leverage), and must ensure that the tested group is being isolated by selecting a n appropriate movement and supporting the patient (see Table 10.5 for more on motor testing ). Behavioral (voluntary malingering or psychogenic) patterns of weakness are notable for a ratcheting or collapsing \200\234give-way \200\235quality rather than a steady level of po wer. A suggestible patient who responds to encourage- ment may demonstrate 5/5 muscle stren gth for a split second before seem- ing to give out \200\224and such is enough to determine that motor pathways are in fact intact. Another hallmark is distractibility, with involunt ary or casually 331 Table 10.2 UMN lesions These are caused by damage to motor pathways anywhere from the motor nerve cells in the pre central gyrus of the frontal cortex (the motor strip) through the internal capsule, brainst em, and spinal cord. Typical characteristics are the so-called \200\234pyramidal \200\235 d istribution of pref- erential weakness involving physiological extensors of the upper limb (shoulder abduction; elbow, wrist, and finger extension, and the small muscles of the hand) and the flexors of the lower limb (hip flexion, knee flexion, and ankle dorsiflexion and e verters). There is little muscle wast- ing and loss of skilled fine finger movements may be greater than expected from the overall grade of weakness. Increased tone (spasticity) deve lops in stronger muscles (arm flexors and leg extensors). It is manifest as resis- tance to passive movement that can suddenly be overcome (clasp-knife feel). There is hyperreflexia: Reflexes are brisk; plantars are upgoing (+ve Babinski sign) clonus (elicited by the ex aminer rapidly dorsiflexing the foot) is more suggestive of an UMN lesion (1 or 2 rhythmic, downward beats of the foot may be normal); a positive Hoffmann \200\231s reflex \200\224p assive flicking of a finger (examiner rapidly flexes a DIP joint) causes neighbor- ing digi ts, particularly the thumb, to briefly flex. UMN weakness affects muscle groups rather than individual muscles. Table 10.3 LMN lesions These are caused by damage anywhere from anterior horn cells in the cord, nerve roots, plex us, or peripheral nerves. The distribution of weak- ness corresponds to those individual mu scles supplied by the involved cord segment, nerve root, part of plexus, or peripheral nerv e. A com- bination of anatomical knowledge, good muscle testing technique, and experience i s needed to distinguish them (e.g. a radial nerve palsy from a C7 root lesion, or a common peroneal nerve palsy from an L5 root lesion). The relevant muscles will generally exhibit l oss of resistance to rapid passive movements ( hypotonia/flaccidity ) and may show spontane - ous involuntary twitching ( fasciculation ). Over time, they will also exhibit loss of bu lk, with atrophic wasting. Reflexes are reduced or absent, the plantar responses remain fle xor (negative Babinski) . 332 Table 10.4 Muscle weakness grading (MRC classification) No muscle Active movement against gravity Active movement Grade 0 Grade 3 contraction Grade 1 Flicker of contraction Grade 4 against resistance Grade 2 Some active movement Grade 5 Normal power (allowing for age) Because Grade 4 covers such a large range of strength, from marked paresis with substantial disability to nearly normal power, it is often sub- divided, with 4 \200\223 , 4 , and 4+ denoting movement against slight, moderate, and stronger resistance respectively. Some exam iners also document 5 \200\223 power as barely below normal. observed strength demonstrably greater than strength on directed confron- tational testing; for example, a patient being able to lift a supposedly plegic leg during testing of balanc e. Sensory deficits: Information about the site of a lesion is conferred by the distributio n of the sensory loss. Additionally, because specific sensory modalities travel in anatomic ally discrete pathways, the pattern/type of sensory loss may convey additional information. For example, pain and temperature sensations travel along small fibers in peripheral nerve s and spinothalamic tracts in the cord and brainstem and are distinct from joint position a nd vibration sense (traveling in fast myelinated fibers in the dor- sal columns of the cord ). Distal, symmetric, length-dependent sensory loss (feet affected more than ankles) sugges ts a polyneuropathy and may involve all sensory modalities or be more selective, depending on the nerve fiber size involved. Individual nerve lesions are identified by the anatomic t erri- tories they innervate, which are more distinctly defined than those of root lesions ( dermatomes), which often show considerable overlap (refer to sec- tion on peripheral nervou s system below). The hallmark of a spinal cord lesion is a sensory level; that is, an area of decreased or absent sensation at and below the lesion (e.g., numbness from the mid-trunk down to the toes), but with normal sensation above. Lateralized cord lesions give rise to a Brown-S quard syndrome, with dorsal column damage on the side of the lesion causing ip silateral loss of joint position sense, and spinothalamic damage causing reduction of pain and temperature sense on the contral- ateral side (the other cardinal feature is ipsilatera l motor involvement). In thalamic and cortical lesions, sensory loss is contralateral to th e lesion and can be confined to more subtle and discriminating sensory functions (pat- tern /texture detection, graphesthesia, stereognosis). y g o o r u e N l Nervous system anatomy The elegance of clinical neurology is a product of nervous system an atomy. Understanding the functions associated with various locations within the central and peripheral nervous system is critical for localization. Although some person-to-person var iability exists, most of the so-called higher corti- cal functions can be mapped to relativ ely specific locations within the cor- tex. (Little annoys a neurologist more than hearing from a colleague that a neurological examination is \200\234nonfocal, \200\235 typically me aning without weakness or sensory loss, when visual system, mental status, or coordination testing may implicate specific areas of brain dysfunction). Gray matter holds neu- ronal ce ll bodies (the processors), organized in nuclei or layered structures, and white matter con sists of myelinated axons (the wiring). Within the white matter, brainstem, spinal cord, an d peripheral nervous system there is limited variability among patients, making localizatio n extremely reliable. 333 Higher functions of the cortex Frontal lobe Hemispheric dominance is defined by the locatio n of Broca \200\231s area, which is responsible for the motor production of speech. The vas t majority of right-handed individuals have their speech production area within the left he misphere, whereas left-handed individuals are split 50:50 between right- and left-hemisphe re dominance. The frontal lobes anteriorly are composed of orbitofrontal and dorsolateral r egions. These areas are involved in olfac- tion, visual interpretation, executive planning, and memory. Also within the frontal lobes are the frontal eye fields (FEF) responsible for initiating saccadic eye movements, the FEF on the left responsible for initiating eye move ments to the right, and vise versa. Thus, an easily observable sign of a frontal stroke (al so visible on imaging studies) is gaze deviation toward the damaged hemisphere (inability to look away) due to damage of the FEF. On the dominant side, Broca \200\231s area is responsible for the motor production of speech, whereas the nondom inant side the frontal lobe controls prosody (voice inflections with questions and statemen ts). Specific damage to Broca \200\231s area will cause stammering, hesitant speech, often with a great degree of frustration as the patient will \200\234know \200\235 what he wants to say but be unable to express himself. Posteriorly in the frontal lobe are the premotor and motor strips. These structures are the control center for voluntary face, head, neck, b ody, and limb movements of the opposite side of the body. Parietal lobe The parietal lobes are primarily sensory structures, acting as the primary in put for various somatosensory systems and providing significant networks for the interpreta tion of the incoming information. A significant portion of parietal lobe function is dedica ted to visuospatial representations \200\224maps \200\224 both of our own bodies and of our surroundings. Hence, a nondominant hemisphere parietal lobe lesion will often cause a hemi neglect syndrome, in which patients do not attend to (ignore) the contralateral side (i.e., dress- ing one half of their body, only speaking to people on one side of the room, etc.). The dominant parietal lobe, particularly Wernicke \200\231s area, is also responsible for much of the \200\234meaning \200\235 of language. Specific damage to Wernicke \200\231s are a can cause a \200\234word salad \200\235 fluent aphasia, with the patient producing string s of nonsense speech devoid of content, unaware that they neither produce nor comprehend ev en simple utterances. Temporal lobe The temporal lobes have a variety of functions including language, memory, be havior, interpretation of visual inputs, and hearing. Within the temporal lobes are the hip pocampi, responsible for consolidation of new memo- ries; damage to them (e.g., from dement ia or anoxia) causes amnesia with short-term memory loss. An epileptic focus located within the temporal lobe will often present as complex partial seizures with patients appearing c onfused and acting strangely. Occipital lobe The occipital lobes are dedicated to visual pathways. Information from the r etina is carried via the optic nerves and optic tracts to the lateral genicu- late nuclei o f the thalami. From there, the optic radiations transmit visual field information to the co ntralateral occipital lobes. Primary visual infor- mation is translated into more highly pr ocessed forms within the occipital lobes, with parallel streams of abstracted information ( color, form, motion, contrast, etc.) being passed along from the initial topographical map of the primary visual cortex. The temporal and parietal lobes assign significance to the st ructures perceived by the occipital lobes. Occipital lobe lesions cause contralateral visua l field loss (i.e., a right occipital lesion causes impaired perception of visual space to the left of fixation, through either eye; the problem is with the TV screen, not the camera s). Bilateral occipital strokes can cause complete cortical blindness (Anton \200\231s synd rome), typically with the patient being unaware of her deficit. It may present with disorie ntation and visual confabulation that may be mistaken for delirium. Isolated occipital lobe strokes are commonly \200\234missed \200\235 by patients as well as well as by providers. The patient may complain of something vaguely wrong with his vision, perhaps in the settin g of a slight orbital headache ipsilateral to the stroke. If visual fields are not examined \200\224the simplest way being a quick screen of finger movements in each quadrant distall y and finger counting in each quadrant more centrally \200\224the patient may go undiagnose d. As occipital lobe infarctions can be an early sign of a threatened basilar artery occlus ion, a missed diagnosis can be disastrous. 334 Deep nuclei: Basal ganglia, thalamus, hypothalamus These extracortical collections of gray matter lie deep within the brain. The basal ganglia predominately control motor function, w ith lesions causing extrapyramidal motor disorders such as parkinsonism (bradykinesia, rest ing tremor, masked facies), chorea (dancing/jerky movements), and athetosis (writhing). Les ions of the nearby subthalamic nucleus may cause the wildly flinging motions of hemiballism us. The anatomy of the thalamus is extremely complex, with many subnuclei, but is best know n clinically as a relay between ascending sensory pathways and the cortex. Lesions typicall y affect contralateral sensory modalities from the face and/or body, with loss of sensation or occasionally a central pain syndrome (Dejerine-Roussy syndrome). Damage to the left tha lamus sometimes produces aphasia, and to the right may produce neglect. The hypothalamus is a deep midline structure at the base of the brain, regulating a number of vital \200\234p rimitive \200\235 homeostatic functions including the biological clock, appetite mechanisms , temperature, and release of pituitary hormones. Various distinct cell populations and fun ctions are again clus- tered into numerous nuclei. y g o o r u e N l Brainstem The brainstem is expensive real estate \200\224a number of vital structures and c rucial pathways confined to a small, densely packed and complex region of anatomy. Divided into three portions \200\224the midbrain (uppermost), the pons (middle), and the medulla (l owermost) \200\224the brainstem consists of long fiber tracts descending from the brain (mo tor and modulatory) or ascending from the body (sensory), and relay circuitry to and from t he cerebellum. It also houses the various nuclei for the individual cranial nerves, as well as structures dealing with pain and its modulation, consciousness, autonomic function, nau sea, balance, and other important somatic functions. Localization in the brainstem is facil itated by identification of damaged cra- nial nerve function. For example, a process affect ing cranial nerves III or IV would occur in the midbrain, VI or VII the pons, and XI the me dulla. Because of the small size and high density of structures, nearby pathways or nuclei are nearly always affected by brainstem lesions, and thus isolated \200\234pure \200\235 c ranial neuropathies are more usually due to a more distal/periph- eral process. The trigemi nal nerve (V) has longitudinally extensive nucleus and fiber tracts, meaning that injury an ywhere from the midbrain to the upper spinal cord could result in facial sensory symptoms. 335 Cerebellum The cerebellum serves as a feedback integrator of complex movements across multi ple joints, assists in coordination of speech output, and is involved in eye movements and balance. Its role in cognition is somewhat obscure. Relatively esoteric or subtle signs of specific cerebellar lesions are beyond the scope of this chapter. In general, due to double -decussation of its prominent pathways, cerebellar lesions will cause ipsilateral incoordin a- tion (dysmetria, ataxia, impaired fine movements, or intentional tremor that worsens as the hand approaches the target). Peripheral/hemispheric lesions tend to affect limbs, and m idline lesions the trunk and balance. In cerebellar injury speech may be slowed, monotonous , jerky/arrhythmic, and/or slurred.