A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.

OBJECTIVE: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. METHODS: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. RESULTS: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). CONCLUSIONS: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.

Infectious myositis. A tropical disease steals out of its zone.

Infectious myositis is an acute infection of skeletal muscle that is increasing in prevalence with the increased incidence of HIV disease. Typical presentation is asymmetric swelling of an isolated muscle, with exquisite pain and fever. Results of laboratory studies are usually nonspecific, but magnetic resonance imaging of the affected area suggests the diagnosis. Muscle biopsy and direct identification of the pathogen on tissue culture are required, because the list of potential pathogens is long. With prompt treatment, most patients achieve complete resolution and return to their preinfection level of health.

Caudate infarcts.

Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

Pressure-related torticollis: an unusual manifestation of pseudotumor cerebri.

A 9-year-old boy with pseudotumor cerebri who presented with neck pain and an accompanying torticollis is described. The patient exhibited bony abnormalities of the upper cervical spine and facial asymmetry that suggested a congenital torticollis. Reduction of the increased cerebrospinal fluid pressure by lumbar puncture resulted in a prompt and dramatic resolution of the cervical symptoms and signs. Increased cerebrospinal fluid pressure should be added to the list of those disorders that may give rise to reversible torticollis.

Dissection of the intracranial vertebral artery.

We describe four patients and review prior reports to clarify the clinical, radiographic, and pathologic findings of intracranial vertebral artery (VA) dissection. A 43-year-old man and a 33-year-old woman had chronic bilateral VA dissecting aneurysms. The man had multiple episodes of subarachnoid hemorrhage (SAH) and necropsy showed multiple dissections and defects in the internal elastica. The woman had many brainstem TIAs and strokes during 3 years. Two other patients had SAH and unilateral dissections. Intracranial VA dissection causes four overlapping syndromes: (1) brainstem infarcts are usually due to subintimal dissection extending into the basilar artery, affect younger patients, and often are single fatal events; (2) SAH is due to subadventitial or transmural dissection; (3) aneurysms cause mass effect on the brainstem and lower cranial nerves; and (4) chronic dissections due to connective tissue defects cause extensive bilateral aneurysms and repeated TIAs, small strokes, and SAH.

Dental chair intracerebral hemorrhage.

A 52-year-old woman had a fatal intracerebral hemorrhage after dental manipulation. Normotensive in the past, the initial blood pressure was high but rapidly returned to normal. Necropsy showed no vascular malformation or evidence of hypertensive vascular disease. Clinical and experimental data show that stimulation of trigeminal fibers can cause important changes in blood pressure and pulse.

Limb shaking--a carotid TIA.

Eight patients are described with an unusual form of carotid transient ischemic attack, limb shaking. The basic features included a brief, involuntary, coarse, irregular, wavering movement or tremble involving arm-hand alone, or arm-hand and leg together. In 2 patients limb shaking was the initial manifestation of carotid occlusive disease, and all but one patient had other typical carotid transient ischemic attacks. Major atheromatous carotid occlusive disease was present in all patients on the side opposite the limb movements. Four patients had bilateral carotid occlusive disease. Cerebral ischemia from a carotid territory low-perfusion state may be the pathogenesis of these limb movements, an idea supported by the apparent benefit of surgical revascularization in abolishing or reducing the limb shaking in 6 patients. There was no clinical or EEG evidence to document an epileptiform etiology. Recognition of this uncommon form of carotid transient ischemic attack may be important in the early diagnosis and treatment of carotid occlusive disease.

Neuromuscular transmission defect in inherited polyneuropathy.

A 51-year-old woman with an inherited polyneuropathy had fatiguability and a dramatic historical response to prostigmine. Repetitive motor nerve stimulation produced a prominent decrement of the compound muscle action potential in distal muscles with marked facilitation after brief exercise. Defective neuromuscular transmission paralleled the polyneuropathy in distribution and severity. We hypothesize that deficient release of acetylcholine by regenerating or degenerating nerve terminals likely caused the defect of neuromuscular transmission in this patient.