MRI findings in Susac's syndrome.

BACKGROUND: Susac syndrome (SS) is a self-limited syndrome, presumably autoimmune, consisting of a clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. All three elements of the triad may not be present or recognized, and MR imaging is often necessary to establish the diagnosis. OBJECTIVE: To determine the spectrum of abnormalities on MRI in SS. METHODS: The authors reviewed the MR images of 27 previously unreported patients with the clinical SS triad, and 51 patients from published articles in which the MR images were depicted or reported. RESULTS: All 27 patients had multifocal supratentorial white matter lesions including the corpus callosum. The deep gray nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%) also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of the 51 cases from the literature, at least 32 had callosal lesions. The authors could not determine the presence of callosal lesions in 18 of these patients, and only one was reported to have a normal MRI at the onset of encephalopathy. CONCLUSIONS: The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

Hot feet: erythromelalgia and related disorders.

Erythromelalgia is an extraordinary pain syndrome first described by S. Weir Mitchell in 1878. Episodes of severe burning pain in the distal limbs, accompanied by striking redness and warmth of the skin, are precipitated by heat or activity and can be terminated only by cooling the affected part. Primary erythromelalgia is a sporadic or autosomal-dominant hereditary disorder whose symptoms begin in childhood. Secondary erythromelalgia occurs in association with thrombocythemia, collagen-vascular diseases, diabetes mellitus, peripheral neuropathy, and use of certain drugs. Aspirin is effective for patients with thrombocythemia, but most other cases are very resistant to treatment. The pathogenesis of erythromelalgia has remained puzzling, especially the peculiar switch-like manner in which symptoms are turned on by heat and turned off by cold. Following Ochoa's description of the ABC (angry backfiring C nociceptors) syndrome, it seems plausible to regard erythromelalgia as a problem of sensitized skin polymodal C-fiber receptors. C-fiber threshold to activation by heat would be lowered to 32 degrees C to 36 degrees C; activated C fibers would cause vasodilation via axon reflexes with redness, heat, and swelling. Cooling would bring the nociceptors below threshold. Secondary erythromelalgia may result from humoral factors released from platelets or ischemic tissues or from C-fiber injury in some cases of neuropathy, whereas primary erythromelalgia could be due to a mutation of the capsaicin receptor.

Adult-onset nemaline myopathy: Another cause of dropped head.

A 59-year-old man with severe neck extensor weakness had findings diagnostic of nemaline myopathy on muscle biopsy. Review of the literature shows that dropped head occurs in nearly half of the patients with adult-onset nemaline myopathy. Other leading causes of dropped head syndrome are amyotrophic lateral sclerosis, myasthenia gravis, and isolated neck extensor myopathy.

Neurologic complications of lumbar epidural anesthesia and analgesia.

We reviewed the clinical features of 12 patients with neurologic complications following lumbar epidural anesthesia or analgesia. Eleven patients experienced lumbosacral radiculopathy or polyradiculopathy and, of these, 10 received epidural anesthesia or analgesia and one received subarachnoid injection of medication after intended epidural anesthesia. One patient suffered a moderately severe thoracic myelopathy in the setting of unintended spinal anesthesia. The two patients with more severe polyradiculopathy had severe lumbar spinal stenosis on MRI. The other patients experienced mild to moderate neurologic deficits most often involving the L-2 root, and MRIs, when performed, were unremarkable. EMG on three patients helped to localize the lesions to the lumbosacral roots and to quantify the extent of axonal loss. Ten patients were ambulatory upon discharge from the hospital and had good neurologic outcome. One patient with severe polyradiculopathy did not improve after 4 years and had severe motor axonal loss based upon electrodiagnostic studies. The patient with a thoracic myelopathy was ambulatory 4 months after onset. Although generally a safe procedure with low frequency of complications, lumbar epidural anesthesia or analgesia occasionally causes neurologic sequelae such as radiculopathy or myelopathy. Neurologic complications may be more severe in the presence of spinal stenosis or after inadvertent subarachnoid injection of anesthetic or analgesic agent.

The origin of muscle fasciculations and cramps.

The anatomic site of origin of muscle fasciculations and cramps has been debated for many years. Many authors have argued for a central origin of the abnormal discharges in the anterior horn cells. However, most of the evidence favors a very distal origin in the intramuscular motor nerve terminals. The factors giving rise to these discharges are not well understood. Fasciculations may be related to chemical excitation of motor nerve terminals, whereas cramps may result from mechanical excitation of motor nerve terminals during muscle shortening.

Dihydropyridine receptor mutations cause hypokalemic periodic paralysis.

Hypokalemic periodic paralysis (hypoKPP) is an autosomal dominant skeletal muscle disorder manifested by episodic weakness associated with low serum potassium. Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine (DHP) receptor gene. This receptor functions as a voltage-gated calcium channel and is also critical for excitation-contraction coupling in a voltage-sensitive and calcium-independent manner. We have characterized patient-specific DHP receptor mutations in 11 probands of 33 independent hypoKPP kindreds that occur at one of two adjacent nucleotides within the same codon and predict substitution of a highly conserved arginine in the S4 segment of domain 4 with either histidine or glycine. In one kindred, the mutation arose de novo. Taken together, these data establish this DHP receptor as the hypoKPP gene. We are unaware of any other human diseases presently known to result from DHP receptor mutations.

Idiopathic, progressive mononeuropathy in young people.

We describe six young patients with insidiously progressive, painless weakness in the distribution of a single major lower extremity nerve. No cause could be found despite extensive evaluation, including surgical exploration. At the time of diagnosis, all patients had weakness and three patients had sensory loss. In all cases, electromyography revealed a chronic axonal mononeuropathy without conduction block or focal conduction slowing. Magnetic resonance, computed tomographic, and ultrasound imaging studies did not identify a region of nerve swelling, mass, or compression. At surgical exploration, the nerve appeared atrophic in two patients, indurated in one patient, and normal in two patients. Biopsy specimens obtained from two abnormal nerves revealed either wallerian degeneration or endoneurial fibrosis. The clinical features of these patients comprise an unusual clinical entity with no known cause or treatment.

Wolfram syndrome: evidence of a diffuse neurodegenerative disease by magnetic resonance imaging.

Wolfram syndrome is an autosomal recessive disorder beginning in childhood that consists of four cardinal features: optic atrophy, diabetes mellitus, diabetes insipidus, and neurosensory hearing loss. Aside from these features, the clinical picture is highly variable and may include other neurologic abnormalities such as ataxia, nystagmus, mental retardation, and seizures. We present two unrelated patients with Wolfram syndrome, both of whom had the four cardinal features and several other neurologic abnormalities. MRIs showed widespread atrophic changes throughout the brain, some of which correlated with the major neurologic features of the syndrome.

Subacute, reversible motor neuron disease.

Four patients with a clinical syndrome closely resembling amyotrophic lateral sclerosis recovered completely, without treatment, 5 to 12 months after onset. Electrodiagnostic tests revealed acute and chronic denervation, with normal motor and sensory nerve conduction studies. The CSF was normal, and tests for paraproteinemia, heavy metal intoxication, and systemic illness were negative. Although such cases are rare, the possibility of spontaneous recovery should always be considered when counseling patients with suspected ALS.

Muscle metabolism during fatigue and work.

Metabolic fatigue is a characteristic muscle response to intense exercise that has outstripped the rate of ATP replacement. The accumulation of metabolic by-products, namely hydrogen ions and diprotonated phosphate, interferes with actin-myosin interaction, effectively preserving muscle ATP levels by preventing further ATP hydrolysis. Muscle force and metabolite concentrations return to normal in about 5 minutes. Less intense exercise causes a more subtle, non-metabolic fatigue due to a still-undefined disturbance of excitation-contraction coupling, which can last for several hours. In this type of fatigue, greater effort is required to generate submaximal forces. Endurance exercise is mainly limited by the size of muscle glycogen stores and how efficiently they are used. Endurance training permits an athlete to work aerobically at high rates, consuming a mixture of lipid and carbohydrate fuels. When muscle glycogen is used up, exercise can only continue at the relatively low rate supportable by lipid metabolism. Anaerobic exercise is also limited by subjective factors such as dyspnoea and muscle pain, which have objective determinants. Extremely prolonged exercise can lead to general collapse because of dehydration, hyperthermia, or hypoglycaemia. None of these factors explains the phenomenon of asthenia, a subjective sense of exhaustion that produces no objective impairment of physical performance. The metabolic myopathies are experiments of nature that promise to shed new light on the biochemical basis of muscle fatigue. This will require quantitative studies of the kind provided by topical magnetic resonance spectroscopy, correlating physiology and metabolism in vivo.

Effects of fatiguing exercise on high-energy phosphates, force, and EMG: evidence for three phases of recovery.

Experiments were designed to evaluate the relative contribution of impulse propagation failure, high-energy phosphate depletion, lowered pH, and impaired excitation-contraction coupling to human muscle fatigue and recovery. 31P nuclear magnetic resonance spectroscopy measurements were made on adductor pollicis muscle, together with simultaneous measurements of M-wave, force, and rectified integrated EMG (RIEMG). During fatigue, maximum voluntary contraction force (MVC) fell by 90%, pH fell from 7.1 to 6.4, and phosphocreatine was almost totally depleted. Neuromuscular efficiency (NME = force/RIEMG) was reduced to 40% of control at the end of the fatiguing contraction, and the M wave was reduced in amplitude and prolonged in duration. Following exercise, the M wave returned to normal within 4 minutes. pH, high-energy phosphates, and MVC recovered within 20 minutes. By contrast, neuromuscular efficiency did not recover within 60 minutes. These findings indicate three different components of fatigue. The first is reflected by the altered M wave and indicates impaired muscle membrane excitation and impulse propagation. The second, associated with reduced MVC, correlates with the metabolic state of the muscle (PCr and pH). The third, indicated by reduced NME, is independent of changes in high-energy phosphates and pH and is probably due to impaired excitation-contraction coupling.

Emery-Dreifuss muscular dystrophy with autosomal dominant transmission.

A woman with early-onset, slowly progressive, humeroperoneal muscle weakness had marked restriction of neck flexion with contracture at the elbows. She developed exertional dyspnea at age 25, atrial fibrillation with slow ventricular rate was discovered, and a cardiac pacemaker was implanted. Her father had a similar disorder. There is at least one other report of autosomal dominant transmission of this clinical picture, which had previously only been reported as Emery-Dreifuss muscular dystrophy with X-linked recessive inheritance. Thus, more than one mode of inheritance is possible for this unusual and distinctive form of muscular dystrophy.

Clinical disorders of muscle energy metabolism.

The disorders of muscle energy metabolism can be classified into degenerative (myopathic) and dynamic syndromes. Four dynamic syndromes are currently recognized: 1) defective carbohydrate utilization, due to block of glycogenolysis or glycolysis; 2) defective lipid utilization, due to deficiency of the mitochondrial translocation of long-chain fatty acids (carnitine palmityltransferase deficiency); 3) lactic acidosis, due to defects of mitochondrial electron transport enzymes and possibly other unidentified defects; and 4) abnormal adenine nucleotide metabolism, exemplified by adenylate deaminase deficiency. The way in which the response to exercise is affected by impaired muscle energy metabolism is dependent on the type of metabolic defect. Defective carbohydrate metabolism severely limits the ability for high-intensity and ischemic exercise. The ability to perform prolonged exercise is markedly impaired in dynamic disorders of lipid metabolism. Other disorders, including those of adenine nucleotide metabolism also may have important implications for our understanding of the metabolic phenomena involved in exercise and recovery.

Periodic paralysis and the sodium-potassium pump.

Analysis of the pathophysiology of hypokalemic paralysis, as it occurs in barium poisoning, chronic potassium deficiency, and thyrotoxicosis, suggests that these disorders may have a similar mechanism. An increased ratio of muscle sodium permeability to potassium permeability reduces the ionic diffusion potential, while the resting membrane potential is sustained by an increase of Na-K pump electrogenesis. The result is that potassium entry (the sum of active and passive influx) exceeds potassium efflux; this causes a large shift of extracellular potassium into muscle until the Na-K pump turns off, leading to depolarization and paralysis. The primary defect in familial hypokalemic periodic paralysis, as in the example of barium poisoning, may be a marked reduction of muscle permeability to potassium.