kinetic/postural tremor usually seen in the upper extremities, sometimes involving the head , neck, and voice as well. Generally, it is characterized by low-amplitude, high-frequency movement that can be disabling in its most severe forms. Often, patients identify other fam ily members with similar tremors. More than half of patients will report improvement in the tremor after consumption of alcoholic beverages. Primidone and propranolol are the mainsta ys of therapy for patients with ET. Responses are seen in 50 \200\22375% of patients. Other anticonvulsants are sometimes used (gabapentin, topiramate), and thalamic DBS can be very helpful in severe cases. Non-ET tremor can be difficult to treat. Sometimes weighted silver ware or wrist weights can be used to reduce oscillations. Severe intentional tremor from MS may respond to thalamic DBS. 384 Neuromuscular disease Neuromuscular diseases involve pathologies of the nerve roots, plexus es, nerve axons, myelin sheaths, neuromuscular junctions, and muscles. Patients will compla in of weakness, numbness, or both. Cramping may be present. The pattern of dysfunction is t he clinical key to identifying neuromuscular conditions. Electrophysiology studies (nerve c onduction and electromyog- raphy) serve as an extension of the clinical exam \200\224 they do not replace it ! For example, once a peripheral neuropathy is identified, there is no cl inical means to determine whether the pathology is demyelinating or axonal. A variety of di fferent diseases \200\224often autoimmune \200\224cause demyelinating con- ditions and woul d be treated quite differently than axonal pathologies. A nerve conduction study would iden tify if there were reduced conduction velocities (indicative of demyelination) versus low a mplitudes (signifying axonal loss). The pattern of nerve weakness and numbness is crucial for determining where within the peri pheral nervous system pathology exists. A mononeu- ropathy will give symptoms confined to o ne nerve distribution. A systemic condition causing a polyneuropathy classically affects th e longest nerves first, giving predominantly distal symptoms (toes prior to ankles). The fo llowing section reviews neuromuscular disease from a clinical standpoint. y g o o r u e N l Mononeuropathies These are lesions of individual peripheral and cranial nerves. There are a variety of causes, including trauma, diabetes, heavy metal exposure, infec- tions such as leprosy, and vasculitides. If more than one peripheral nerve is affected, the term mononeur itis multiplex is used. Causes include diabetes, vasculitis, infections, amyloidosis, rheum atoid arthritis, paraneoplastic syn- dromes, and a variety of hereditary diseases. Median n erve C6 \200\223T1 At the wrist (e.g., lacerations; carpal tunnel syn- drome \200\224see Ta ble 10.20): Weakness of abductor pollicis brevis and sensory loss over the radial 3 finge rs and palm. Lesions confined to the anterior interosseous nerve: Weakness of flexion of th e distal phalanx of the thumb and index finger. Proximal lesions (e.g., at the elbow) may s how combined defects. Ulnar nerve C7 \200\223T1 Vulnerable to elbow trauma and at the wrist . Signs: Weakness/wasting of medial (ulnar side) wrist flexors; weakness/wasting of the int erossei (cannot cross the fingers) and medial two lumbricals (claw hand); wasting of the hy pothenar eminence, which abolishes finger abduc- tion and sensory loss over the medial 1 fingers and the ulnar side of the hand. Flexion of fourth and fifth DIP joints is weak. Tre atment: See Table 10.21. With lesions at the wrist (digitorum profundus intact), claw hand is more marked. Radial nerve C5 \200\223T1 This nerve opens the fist. Damaged by compressio n against the humerus (commonly seen with humeral fractures). Test for wrist and finger dro p with elbow flexed and arm pronated. Sensory loss: Variable; test dorsal aspect of root of thumb. Sciatic nerve L4 \200\223S2 Damaged by pelvic tumors or fractures to pelvis or femu r. Lesions affect the hamstrings (knee flexors) and all muscles below the knee (foot drop), with loss of sensation below the knee laterally. Common peroneal nerve L4 \200\223S2 Frequ ently damaged as it winds round the fibular head by trauma or tight-fitting casts. Lesions lead to inability to dorsiflex the foot (foot drop), evert the foot, extend the toes \200 \224and sensory loss over dorsum of foot. Tibial nerve S1 \200\2233 Lesions lead to an inab ility to stand on tiptoe (plantar flexion), invert the foot, or flex the toes. Sensory loss over the sole. 385 Table 10.20 Carpal tunnel syndrome: The most common mononeuropathy Nine tendons and the median nerve compete for space within the wrist. Compression is common , especially in women who have narrower wrists but similar-sized tendons to men. The patien t: Aching pain in the hand and arm (especially at night) and paresthesias in the thumb, ind ex, and middle fingers, all relieved by dan- gling the hand over the edge of the bed and sh aking it. Some patients experience referred pain into the forearm and shoulder. There may b e sensory loss and weakness of abductor pollicis brevis with or without wasting of the then ar eminence. Light touch, two-point discrimination, and sweating may be impaired. Associati ons: Pregnancy, rheumatoid arthritis, DM, hypothyroidism, dialy- sis, trauma. Tests: Neurop hysiology helps by confirming the lesion \200\231s site and severity (and likelihood of imp rovement after surgery). Maximal wrist flexion for 1 min (Phalen \200\231s test) may elicit symptoms but is unreliable. Tapping over the nerve at the wrist induces tingling (Tinel \200\231s test; also rather nonspecific). Treatment: Splinting of the wrist for 3 \200\2236 months may help. If not, local steroid injection may be temporizing. Surgical decompressio n (tradi- tional or minimally invasive) is quite effective in the long run, but at the expe nse of slight reduction in grip strength and initial immobility during recovery. Table 10.21 Managing ulnar mononeuropathies from entrapments The ulnar nerve is in an anatomically precarious position and is subject to compression at multiple sites around the elbow. Most commonly, compression occurs at the epicondylar groov e or at the point where the nerve passes between the two heads of the flexor carpi ulnaris mus- cle (true cubital tunnel syndrome ). Trauma can easily damage the nerve against its bo ny confines (the medial condyle of the humerus \200\224the \200\234funny bone \200\235). No rmally, the ulnar nerve suffers stretch and compression forces at the elbow that are modera ted by its ability to glide in its groove. When normal excursion is restricted, irritation ensues. This may cause a vicious cycle of perineural scarring, consequent loss of excursion , and progres- sive symptoms \200\224without there being any antecedent trauma. Rest and av oiding pressure on the nerve helps but if symptoms continue, nighttime soft elbow splinting (to prevent flexion to >60 degrees) is warranted for a few months. For chronic neuropathy associated with weakness, or if splinting fails, a variety of surgical procedures have been tried. For moderately severe neuropathies, decompressions in situ may help initially but s ubsequently fail. Medial epicondylectomies are effective in 50% (there is a high rate of re currence). SC nerve reroutings (trans- positions) may be tried. IM and submuscular transpos itions are more complicated, but the latter may be preferable. Compressive ulnar neuropathi es at the wrist ( Guyon \200\231s canal \200\224between the pisiform and hamate bones) are less common, but they can also result in disability. Thoracic outlet compression is anothe r cause of a weak, numb hand. Electromyography (EMG) helps define the anatomic site of lesi ons. 386 Polyneuropathies Polyneuropathies are generalized disorders of peripheral nerves (includ- i ng cranial nerves) whose distribution is usually bilaterally symmetrical and widespread \200\224typically a distal pattern of muscle weakness and sensory loss (known as \200\234st ocking-glove anesthesia \200\235). They may be classified by time course (acute or chronic) , by the functions disturbed (motor, sensory, autonomic, mixed), or by the underlying patho logy (demyelination, axonal degeneration, or both). Guillain \200\223Barr syndrome (GBS) , for example, is a subacute, predominantly motor, demyelinating neuropathy, whereas chroni c alcohol abuse leads to a chronic, initially sensory then mixed, axonal neu- ropathy. Diff erential based on motor vs. sensory predominance is given in Table 10.22 and a more thoroug h list in Table 10.23. Symptoms Sensory neuropathy: Numbness; \200\234feels funny \200\235 ; tingling or burn- ing sensations often affecting the extremities first ( \200\234stocking -glove \200\235 distribu- tion). There may be difficulty handling small objects such as a n eedle. Motor neuropathy: Often progressive (may be rapid) weakness or clumsi- ness of the h ands; difficulty walking (falls; stumbling); respiratory difficulty. Signs are those of an LMN lesion: Wasting and weakness most marked in the distal muscles of hands and feet (foot or wrist drop). Reflexes are reduced or absent. Involvement of the respiratory muscles may be shown by a diminished vital capacity. Cranial nerves: Difficulties swallowing; speaking; double vision; changes in facial sensation, facial weakness. Diagnosis The history is vita l; make sure you are clear about the illness \200\231s time course, the precise nature of t he symptoms, any antecedent or associ- ated events (e.g., gastrointestinal or respiratory s ymptoms preceding GBS, weight loss in cancer, arthralgia from a connective tissue disease), travel, sexual history (infections), alcohol use, medications, and family history. Pain is typical of neuropathies due to DM or alcohol. Examination: Do a careful neurological exami nation looking particularly for lower motor signs (weakness, wasting, reduced or absent ref lexes); any sensory loss should be carefully mapped out for each modality. Make use of a pe ripheral nerve/ myotome/dermatome chart, such as those presented earlier in this chapter, t o assist in localization (Table 10.5; Figures 10.3 and 10.4). Do not forget to assess the a utonomic system and cranial nerves. Look also for signs of trauma (e.g., finger burns) indi cating reduced sensation. Scuff marks on shoes may suggest foot drop. If there is palpable nerve thickening, think of leprosy or Charcot \200\223Marie \200\223Tooth. Examine other sy stems for clues to the cause, such as for signs of alcoholic liver disease. Tests Complete blood count, glucose, hemoglobin A1C, LFT, thyroid function tests, B 12 , protein electroph oresis, ANCA (p- & c-), antinuclear antibodies (ANA), CXR, urinalysis, and consider a LP in the appropriate clinical setting (concern for GBS or chronic inflammatory demyelinating po lyradiculoneuropathy [CIDP]). In a patient with a distal sensory neu- ropathy and no clear cause, obtain a glucose tolerance test to identify patients in a \200\234prediabetic \200 \235 state (which is a significant cause of peripheral y g o o r u e N l 387 Table 10.22 Motor vs. sensory polyneuropathy Mostly motor GBS Lead poisoning Charcot \200\223Marie \200\223Tooth syndrome Mostly sensory Diabetes mellitus Uremia Leprosy Table 10.23 Causes of polyneuropathies Inflammatory GBS, CIDP, sarcoidosis Metabolic Diabetes mellitus, renal failure, hypothyroid ism, hypoglycemia, mitochon- drial disorders Vasculitides Polyarteritis nodosa, rheumatoid arthritis, Wegener \200\231s granulomatosis Malignancy Paraneoplastic syndromes (especially small cell lung cancer), poly- cythemia vera Infections Leprosy, syphilis, Lyme disease, H IV Vitamin deficiencies and excesses Lack of vitamins B 1 , B 6 , B 12 (alcoholics), folate ; also excess of B 6 (>100 mg/d) Inherited Refsum \200\231s syndrome, Charcot \200\223Marie \200\223Tooth syndrome, porphyria, leu- kodystrophy (and many more) Toxins Lead, arsenic D rugs Alcohol, cisplatin, isoniazid, vincristine, nitrofurantoin. Less frequently: Metronida zole, phenytoin Others Paraproteinemias including multiple myeloma, amyloidosis, prediabeti c states (impaired glucose tolerance) neuropathy). Consider specific genetic tests for inherited neuropathies (e.g., Charcot \200 \223Marie \200\223Tooth syndrome), lead levels, and antiganglioside antibod- ies. Nerve con duction studies are necessary for distinguishing demyelinating from axonal neuropathies. Tr eatment Treat the underlying cause if possible (e.g., withdraw precipi- tating drug; tight glucose control in diabetes). Involve physical therapists and occupational therapists. Care of the feet and shoe choice is important in sensory neuropathies to minimize trauma and su bsequent disability. In GBS and CIDP, IV immunoglobulin helps. Steroids and other immunosup - pressants may help vasculitic neuropathy. Although there are no treatments available to i mprove the negative symp- toms of numbness/sensory loss, there are a variety of strategies for managing the positive , painful symptoms of neuropathy such as paresthesia (burning, ti ngling), hyperesthesia (increased pain sensitivity), or allodynia (nonpainful stimuli being perceived as painful). Tricyclic antidepressants (particularly nortriptyline, which is ine xpensive and has a low number-needed-to-treat), serotonin-norepinephrine reuptake inhibitor (SNRI) drugs, and many of the anticonvulsants (gabapentin; pregabalin may be preferred due to relatively benign risk profiles) are useful for this purpose. NSAIDs tend not to help m uch, but the combination mu-opioid agonist/norepinephrine reuptake inhibitors, such as tram adol and tapentadol, may be useful. Chronic opioid therapy can be beneficial for neuropathi c pain, but with attendant risks of tolerance, dependency, etc. Where pain is peripherally mediated, topical treatments (lidocaine patches or creams) should be tried. A high-potency 388 capsaicin patch preparation can result in prolonged pain relief through destruction of unmy elinated C-fibers. y g o o r u e N l Bell \200\231s palsy An idiopathic palsy of the facial nerve (VII) resulting in a unilatera l facial weakness or paralysis. Other causes of a facial palsy must be excluded before a di agnosis of Bell \200\231s palsy is made. Possible etiologies for Bell \200\231s palsy inclu de a viral neuropathy (HSV1 has been implicated) and idiopathic inflammation. Incidence 20 /100,000/yr; risk increases in pregnancy (three-fold) and dia- betes ( five-fold). Symptoms Onset of facial weakness is rapid and may occur with or be preceded by pain below the ear. Weakness worsens for 1 \200\2232 d before stabi- lizing, and pain resolves within a few da ys. Accompanying subtle trigeminal sensory loss may be noted. Any more dramatic trigeminal loss or any other accompanying cranial neuropathies must prompt a search for underlying eti ol- ogy. Symptoms and signs are unilateral. If bilateral, consider other diagno- ses (e.g., sarcoidosis, infiltrative meningeal disease, Lyme disease; see Table 10.24). Patients will experience weakness of the face, including the perio- cular muscles (difficulty closing th e eye), drooling, impaired taste on the anterior tongue, and hyperacusis (the perception of loud sounds due to a paralysis of the stapedius muscle that normally dampens sounds). Natu ral history Those patients with incomplete paralysis and no axonal degeneration typically r ecover completely within a few weeks (approxi- mately 85% of patients with Bell \200\231s p alsy). Those with complete paralysis nearly all fully recover too but 15% have axonal dege neration. Recovery frequently begins only after 3 months, may be incomplete, fail to happen at all, or else will be complicated by the formation of aberrant reconnections producing s ynkinesis (e.g., eye blinking is accompanied by unintentional syn- chronous upturning of th e mouth, or smiling accompanied by involuntary eye closure). Misconnection of parasympathet ic fibers can produce so-called crocodile tears, when eating stimulates unilateral lacrimat ion. Cutting the tympanic branch of IX solves this problem (rarely needed). The House-Brack mann scale is commonly used to score patients with Bell \200\231s palsy and can prognostica te recovery. The scale has six grades (1 \200\2236), with grade 1 being normal and grade 6 describing a patient with no movement whatsoever. Tests Electroneurography at 1 \200\2233 w ks can predict delayed recovery by identi- fying axonal degeneration but does not influence management. MRI and LP help rule out other diagnoses (only needed in atypical presenta- ti ons, such as bilateral Bell \200\231s palsy or a facial nerve palsy in the presence of conc omitant cranial neuropathies). In the appropriate setting, consider testing for other disor ders, such as Lyme. Management If presentation is within 6 d of onset, prednisone (1 mg/ kg /d for 5 \200\22310 d) is relatively safe and probably effective in improving facial functi on outcomes in patients. Acyclovir, however, is considered by the American Academy of Neuro logy Practice Guidelines to be safe (in combi- nation with prednisone) and possibly effecti ve in treating Bell \200\231s palsy. Protect the cornea with artificial tears, lubrication, or overnight taping or moisture chambers if there is any evidence of drying. If ectropion is severe, lateral tarsorrhaphy (partial lid-to-lid suturing) can help. 389 Table 10.24 Other causes of a VII nerve palsy Infection Ramsay Hunt syndrome (cephalic herpes zoster). This is a peripheral facial nerve palsy acco mpanied by a painful erythematous vesicular rash in the ear (zoster oticus) or in the mouth , often with vertigo. (Famciclovir 500 mg/8 h PO + prednisolone may be indicated.) Lyme disease HIV Meningitis Polio TB Chronic meningitis (e.g., fungal) Brainstem lesions Brainstem tumor Stroke MS Cerebellopontine angle lesions Acoustic neuroma, meningioma Systemic disease Diabetes mellitus Sarcoidosis (facial palsy is the most common CNS sign of sarcoidosis) GBS ENT and other rare causes Orofacial granulomatosis \200\224recurrent VII palsies Parotid tumors Cholesteatoma Otitis media Trauma to skull base Pregnancy/delivery, via intracranial hypotension Neuromuscular junction disorders Myasthenia gravis (MG) is an antibody-mediated, autoimmune disease with too few functioning acetylcholine receptors on muscle, leading to muscle weak ness. Antiacetylcholine receptor antibodies are detectable in 80 \200\22390% of patients an d cause depletion of functioning postsynaptic recep- tor sites. A fraction of the remainder will have antibodies to muscle specific kinase, MuSK. Presentation: Can present at any age as worsening muscular fatigability. If <50 yrs, myasthenia is more common in women, associ ated with other autoimmune diseases and thymic hyperplasia. >50 yrs, it is more common in m en and associated with thymic atrophy or, rarely, a thymic tumor. Muscle groups commonly af fected (most likely first): Extraocular, bulbar, face, neck, limb girdle, trunk. Look espec ially for ptosis, diplopia, \200\234myasthenic snarl \200\235 on smiling. On counting aloud to 50, the voice weakens. Reflexes are nor- mal. Weakness may be exacerbated by pregnancy, infection, overtreatment, change of climate, emotion, exercise, gentamicin, opiates, tetra cycline, qui- nine, quinidine, procainamide, and many other medications. Associations: Thym ic tumor, hyperthyroidism, rheumatoid arthritis, SLE. Diagnosis: In the clinically appropri ate situations, obtain an antiacetylcholine receptor antibody titer and anti-MuSK if normal . Although the titer itself does not correlate with disease severity, a positive test is hi ghly suggestive, and the rise or fall in titer can be used to track the success of treatmen t. 390 Additional tests include a repetitive stimulation EMG to look for decremen- tal responses, a single-fiber EMG to look for \200\234jitter, \200\235 and, more rarely, the Tensilon tes t. This pharmacologic test uses the administration of edropho- nium (an anticholinesterase) to determine whether a patient \200\231s symptoms would improve with more acetylcholine at a neuromuscular junction. The test is difficult to assess, somewhat nonspecific, and has s ignificant associ- ated risks (bradycardia, e.g.) and hence is rarely used. Once the diagno sis of MG is established, a CT scan of the chest is obtained to rule out thymic tumors. In patients with MG even without thymic tumors, thymectomy can cause remission or significant improvement and are worth considering in patients who are suitable surgical candidates. Tre atment options: Symptomatic control with an anticholinesterase (e.g., pyridostigmine 60 \200\223450 mg/24 h PO) taken through the day. Side effects include diarrhea, salivation, l acrimation, vomiting, miosis, and even weak- ness. Immunosuppression with prednisone, azath ioprine, cyclosporin, and mycophenolate have all been utilized with success. Also, both pla smaphere- sis and IVIg have been used on 2 \200\2234 wk schedules for patients with difficu lt to control symptoms or in patients suffering from myasthenic crises. Myasthenic crisis i s characterized by weakness significant enough to cause respiratory compromise. This occurs in 10 \200\22320% of patients at some time in the course of their disease and can be trigg ered by preceding infections. Plasmapheresis is commonly used to treat patients in crisis. y g o o r u e N l Lambert \200\223Eaton myasthenic syndrome This typically occurs in association with small c ell lung cancer (Lambert \200\223 Eaton syndrome) or, less commonly, with other autoimmune disease. Unlike MG, it affects especially proximal limbs and trunk (rarely the eyes), there is hypo reflexia, only a slight response to edrophonium, repeated muscle contraction may l ead to increased muscle strength and reflexes, and it is the presynaptic membrane that is a ffected (the carcinoma provokes production of antibodies to Ca 2+ channels). Other causes o f muscle fatigability Polymyositis, SLE, botulism, Takayasu \200\231s disease (fatigability of the extremities due to ischemia from vasculitis). 391 Myopathies Signs and symptoms Muscle weakness Rapid onset suggests a toxic, drug, or metabo lic cause. Excess fatigability (weakness increases with exercise) may suggest MG versus sto rage disease myopathy. Myotonia (delayed mus- cular relaxation after contraction, e.g., una ble to release grip or rapidly let go of a handshake) is characteristic of myotonic disorde rs. Spontaneous pain at rest occurs in inflammatory disease, as does local tenderness. Pain on exercise suggests ischemia or metabolic myopathy (e.g., McArdle \200\231s dis- ease). F asciculation (spontaneous, irregular, and brief contractions of part of a muscle) suggests anterior horn cell or root disease. Look carefully for evidence of systemic disease. Tests: Consider EMG with or without muscle biopsy and investigations relevant to systemic causes (e.g., TSH). Many genetic disorders of muscle can be detected by DNA analysis, and muscle b iopsy is now reserved for when genetic tests are nondiagnostic (e.g., Duchenne \200\231s or myotonic dystrophy). There are five main categories of myopathy 1 Muscular dystrophies are a group of genetic di seases with progressive degeneration and weakness of specific muscle groups. The primary ab nor- mality may be in the muscle membrane. Secondary effects are marked variation in size of individual fibers and deposition of fat and connective tissue. The mos t common is Duchenne \200\231s muscular dystrophy (sex-linked recessive \200\22430% from sp ontaneous mutation) and is (almost always) con- fined to boys. The Duchenne gene is on the short arm of the X chromo- some, and its product, dystrophin, is absent (or present in only very low levels). Serum creatine kinase is raised >40-fold. It presents usually around 4 y rs of age with increasingly clumsy walking, progressing to difficulty in standing and respi ratory failure. Some survive beyond 20 yrs. There is no specific treatment. Genetic counsel ing is vital. Fascioscapulohumeral mus- cular dystrophy (Landouzy \200\223Dejerine) is almo st as common. Inheritance: Autosomal dominant (4q35). Typical age of onset: 12 \200\22314 y rs. Early symp- toms: Inability to puff out the cheeks, difficulty raising the arms above t he head (e.g., changing light-bulbs). Signs: Weakness of face, shoulders, and upper arms (o ften asymmetric with deltoids spared), with or without foot-drop and/or winging of the scap ula. 20% of patients will need a wheelchair by 40 yrs. 2 Myotonic disorders are characterized by myotonia (tonic spasm of muscle). Muscle histolog y shows long chains of central nuclei within the fibers. The chief disorder is myotonic dys trophy (autosomal dominant). Typical onset : 25 yrs with weakness (hands, legs, sternocleid omastoids) and myotonia. Muscle wasting and weakness in the face results in a long, haggard appear- ance. Other features : Cataracts, frontal baldness (men), atrophy of testes or ova ries, cardiomyopathy, mild endocrine abnormalities (e.g., DM), and mental impairment). Most patients die in middle age of intercurrent ill- ness. Genetic counseling is important. 3 Acquired myopathies of late onset are often a manifestation of systemic dis- ease. Look c arefully for evidence of carcinoma, thyroid disease (especially hyperthyroidism), Cushing \200\231s disease, hypo- and hypercalcemia. 4 Inflammatory disorders: Inclusion-body myositis, polymyositis, dermato- myositis, other auto-immune myopathies. 5 Toxic myopathies: Alcohol, statins (etiology may be partially auto-immune), steroids, chl oroquine, colchicine, procainamide, zidovudine, vincristine, cyclosporin, hypervitaminosis E, cocaine. Myelopathies The time course of symptom onset is critical for evaluating patients with myel opathic spinal cord symptoms (UMN weakness, a sensory level, and/ or bowel/bladder dysfunct ion). In the acute setting, compressive lesions must be ruled out because of the urgent ind ication for surgical interven- tion. Traumatic spinal cord injuries are currently treated w ith massive doses of steroids, while nontraumatic, noncompressive myelopathies are evalu- a ted and treated very differently. Certain facts about the patient \200\231s history are cri tical for determining the etiology of the myelopathy. For example, a patient with a T10 sen sory level and spinal cord dysfunction after an angiogram most probably has suffered an ant erior spinal artery occlu- sion and spinal infarct due to disruption of blood supply in the artery of Adamkiewicz. Differential of noncompressive myelopathy Acute and subacute pathol ogies include arterial infarct, venous hypertension (with or without infarct), transverse m yelitis, MS, neuromyelitis optica, spinal cord ischemia related to spinal AV malformations, fistulas, and various spinal tumors (pri- mary and metastatic). A gadolinium-enhanced MRI of the spine and brain and LP can be used to identify to causative process. Evidence of inf lamma- tion (enhancing lesion on MRI, pleocytosis, elevated protein, oligoclonal bands or I gG Index) supports the diagnosis of TM, MS, or NMO. In cases where an acute myelopathy has no clear cause, a spinal angiogram must be considered if a vascular malformation is suspect ed 392 Space-occupying lesions in the brain Signs Features of \206\221 ICP, evolving focal neurol ogic symptom (Table 10.25), seizures, false localizing signs, cognitive or behavioral chang e and local effects (e.g., proptosis). Raised ICP: Headache, vomiting, papilledema (only in 50% of tumors), altered consciousness (the most common finding in patients with \206\221 ICP). Seizures: Seen in about 50% of tumors. Suspect in all adult-onset seizures, especiall y if focal or with a localizing aura or postictal weakness (Todd \200\231s palsy). False lo calizing signs: These are caused by \206\221 ICP. Cranial nerve VI palsy is most common du e to its long intracranial course. Subtle personality change: Irritability, lack of applica tion to tasks, lack of initiative, socially inappropriate behavior may be seen early in the process, but are nonspecific. Causes Tumor (primary or secondary), aneurysm, abscess (25% multiple), chronic subdural hematoma, granuloma (e.g., tuberculoma), cyst (e.g., cysticerco sis, arachnoid). Tumor histology: 30% secondary (breast, lung, melanoma; 50% multiple). Pri maries include astrocytoma, glioblastoma multiforme, oligo- dendroglioma, ependymoma (all < 50% 5-yr survival), cerebellar hemangio- blastoma (40% 20-yr survival), meningioma (general ly benign). Differential diagnosis Stroke, head injury, vasculitis (SLE, syphilis, PAN, gia nt cell arteritis, etc.), MS, encephalitis, postictal (Todd \200\231s palsy), metabolic, or electrolyte disturbances. Also, obstructive hydrocephalus (e.g., from colloid cyst of the third ventricle), venous sinus occlusion, and idiopathic intracranial hypertension. Tests C T; MRI (good for posterior fossa masses). Consider biopsy. Extreme caution with LPs (perfor med only if absolutely necessary) due to risks of cerebellar herniation through the foramen magnum) \200\224see discus- sion above. Tumor management Benign: Complete removal if possi ble but some may be inaccessible. Malignant : Complete removal of gliomas is difficult as r esec- tion margins are rarely clear, but surgery does give a tissue diagnosis and allows de bulking pre-radiotherapy. If a tumor is inaccessible but causing hydrocephalus, a ventricul o-peritoneal shunt may be used to reduce ICP. Radiotherapy is used postop for gliomas or me tastases and as sole therapy for some tumors if surgery is impossible. Chemotherapy is used in gliomas with limited benefit. Intracranial, chemotherapy-impregnated wafers have improv ed outcome somewhat. Dexamethasone 4 mg/8 h PO for vasogenic cerebral edema. Prophylactic a dministration of antiepileptics in patients with newly diagnosed brain tumors is not recomm ended due to a lack of efficacy and the presence of side effects. Enzyme-inducing antiepile ptics may reduce effectiveness of certain chemotherapeutic agents. Prognosis Complete remov al of a benign tumor achieves cure but the prognosis of those with malignant tumors is poor . y g o o r u e N l 393 Table 10.25 Localizing signs Temporal lobe Seizures (complex partial automatisms), hallucina- tions (smell, taste, so und, d j vu ), complex partial with automatisms, dysphasia, field defect (contralateral upper quadrantanopia), forgetful- ness, psychosis, fear/rage, hypersexuality. Frontal lobe Hemiparesis, seizures (focal motor seizures, i.e., aversive seizures involving head and eye s), personality changes (indecent, indolent, indiscreet), positive grasp reflex (fingers dr awn across palm are grasped) significant only if unilateral, aphasia (Broca \200\231s area) , loss of smell unilater- ally. Orbitofrontal syndrome: Lack of empathy, disinhibition, dim inished social skills, overeating, rash actions (mania), unconscious imitation of postures observed in others. Parietal lobe Hemisensory loss, diminished two-point discrimination, as tereognosis (inability to recognize object in hand by touch alone), sen- sory inattention, aphasia, Gerstmann \200\231s syndrome (i.e., left \200\223right disorien- tation), finger a gnosia, acalculia, and agraphia). Occipital lobe Contralateral visual field defects (homony mous hemi- anopia); hallucinations such as palinopsia (persisting or recurring images, once the stimulus has left the field of view). Cerebellum ( \200\230DASHING \200\231) D ysdiado chokinesis, a taxia (truncal), s lurred speech, h ypotonia, i ntention tremor, n ystagmus, g ait abnormality. Dysdiadochokinesis is impaired rapidly alternating movements (e.g., pron ation \200\223supination). Cerebellopontine angle Usually vestibular schwannoma. Ipsilatera l deafness; nystagmus; reduced corneal reflex, facial weakness; ipsilateral cerebellar sign s, papilledema, and cranial nerve VI palsies. Midbrain (e.g., pineal gland tumors or midbra in infarction) Failure of up or down gaze; dissociated pupil responses, with constriction o n near gaze but not to light; convergence retraction nystagmus on attempted upgaze. 394 Neuroradiology Fast-moving technological advances in neurological imaging have revolu- tion ized neurological diagnosis and treatment, shedding light where there once was darkness \200\224but sometimes generating more heat than light. CT works by identifying x-ray attenu ation of materials, measured in Hounsfield units (HU) (e.g., bone +1,000, water 0, and air \200\2231,000 HU). The x-ray attenuation of a pixel is revealed as a shade of gray. At the extremes, high attenuation is white and low attenuation is black. The attenuation of biolo gical soft tissues is in a narrow range from about +80 for blood and muscle, to 0 for CSF, and down to \200\223100 for fat. IV contrast may be given, demonstrating initially an angi ographic effect, the high attenuation contrast in the vessels making them appear white. Lat er, if there is a defect in the blood \200\223brain barrier, as with neoplasms or infection , contrast will extravasate, giving an enhancing white area in the cerebrum or cerebellum. Some intracranial components do not have a blood \200\223brain barrier and thus will enhanc e (e.g., the pituitary gland and choroid plexus). Compared to MRI, CT is good at showing ac ute hemorrhage and fractures and is much easier to perform in ill or anesthetized patients \200\224so it is invalu- able in emergencies. Modern scanners can obtain a whole head view in seconds, and there are basically no contraindications to a noncontrast scan. Fresh blood is of higher attenuation (whiter) than brain tissue. Attenuation of hematomas declines as hem oglobin breaks down so that a subacute subdural hematoma at 2 wks may appear isodense to ad jacent brain, mak- ing it difficult to detect. A chronic subdural hematoma will be of relat ively low attenuation. CT is commonly performed in acute stroke to exclude hemorrhage (befo re giving thrombolytics). An area of ischemia will not show up distinctly for several hours or so, and will appear as low-attenuation cytotoxic edema (intracellular edema mainly conf ined to the gray matter). Tumors and abscesses may share radiographic features \200\224ring -enhancing mass, surrounding vasogenic edema, and mass effect. Vasogenic edema is extracell ular and spreads through the white matter. Mass effect can cause compression of the sulci a nd ipsilateral ventricle. It may also cause subfal- cine, transtentorial, or tonsillar hern iation. One indication for CT scan is acute, severe headache. If there is concern about sub arachnoid hemorrhage, a noncontrast CT may show acute blood. Even if it does not, it will s how if the basal cisterns are normal and therefore LP is probably safe. In MRI, an image is made by disturbing an atomic nucleus in a strong mag- netic field by using a radiofrequenc y pulse at the resonant frequency and detecting the signal as the nucleus (usually hydrogen ) returns to equilib- rium. The resulting noninvasively obtained anatomic and pathological infor- mation is unrivaled, but the technique has drawbacks as well (Table 10.26). The chie f clinically useful image sequences are: \212T1-weighted images: Give good anatomical deta il to which the T2 image can be compared/related. Fat is brightest ( \206\221 signal inten sity) other tissues are darker to varying degrees. Flowing blood appears black ( \200\234fl ow voids \200\235). Bone is dark. Gadolinium contrast agent can be given to \200\234enhance \200\235 vascu- lar lesions or areas of blood-brain barrier breakdown. y g o o r u e N l \212T2-weighted images: These provide the best detection of pathology, with most pathology having some edema fluid and therefore appearing white. Fat and fluid appear brightest. Aga in, fat is bright and bone is dark. \212FLAIR or TIRM: These sequences are similar to T2-weighted images and highlight patholo gy far better but remove the bright signal of CSF, which might otherwise obscure small lesi ons adjacent to sulci or ventricles. \212HEME, gradient echo, or susceptibility weighted i maging: All these sequences highlight blood products (or calcium deposits) as black. They a re very sen- sitive to the point of picking up previously asymptomatic \200\234microbleeds \200\235 in amyloidosis or mild head trauma but tend to \200\234overcall \200\235 the size of small lesions. 395 \212DWI and apparent diffusion coefficient (ADC): Most useful for revealing and dating acu te strokes. DWI imaging will reveal acute cytotoxic injury (ischemic infarction) as bright signal within minutes of onset, out to 14 d. ADC will reveal ischemic injury as dark signa l out to 7 d. \212Perfusion weighted imaging: Serial slices timed around injection of gado- linium contr ast medium reveal areas of the brain that are oligemic. In the setting of a stroke, an area of reduced blood flow without correspond- ing DWI brightness is \200\234at risk \200\235 b ut not yet infarcted and thus potentially salvageable. Often an \200\234ischemic penumbra \200\235 surrounds an area of acute stroke. \212MRA, MRV: MR scanners can reveal vasculature through various tech- niques, each with i ts own advantages and limitations. In general, images obtained from noncontrast studies are related to flow , rather than ana- tomic lumen size. MRV and neck MRA studies are best per formed with contrast enhancement, but MRA of the Circle of Willis is adequately obtained wi thout contrast. \212Other: A host of other specialized MR techniques have been developed that can highligh t specific anatomy and pathology. MR neurography can reveal peripheral nerves and plexus, d iffusion tensor imaging can high- light the integrity of white matter tracts, and morphomet ry and other volumetric imaging can reveal specific areas of atrophy or hypertrophy (often referenced to a standardized \200\234brain map \200\235). Novel sequences can reveal the ot herwise undetectable early gray matter involvement of MS, as well as clinically asymptomati c white matter lesions. MR spectroscopy can show us constituent molecular components of the brain in specific regions of interest (distinguishing, e.g., areas of demyelination from a reas of tumor or of cell death or of abscess). Functional MRI techniques can reveal regiona l brain activation in real time, by way of detecting changes in regional blood flow or bloo d oxygenation status. In PET and SPECT nuclear medicine techniques, images are created by detection of the decay of radioactive atoms attached to an injected molecu- lar label. PET has superior spatial an d far superior temporal resolution, but generally requires an on-site accelerator for gener ating isotopes. Areas of hypo- or hypermetabolism can reveal seizure foci, distinguish absc ess from tumors, or reveal patterns suggestive of specific types of dementia. Specific labe ls have been developed that bind amyloid- or dopamine-producing neu- rons, of potential use in Alzheimer \200\231s and Parkinson \200\231s diseases, respectively. Table 10.26 Advantages and disadvantages of MRI imaging Advantages of MRI Nonionizing radiation Shows vasculature without Disadvantages of MRI High cost Claustrophobia (in magnet tunnel for 15 \200\22360 min \200 \224sedation may be needed) contrast Images can easily be produced in any plane, e.g., sagittal or coronal Motion artifact and longer time for image acquisition Visualization of posterior fossa Unhelpful in imaging calcium Unsuitable for those with fer- romagnetic foreign bodies (pace makers, CNS vascular clips, cochlear implants, valves, shrapnel, etc.)