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A 79-year-old man was referred to the neuromuscular clinic for evaluation of severe polyneuropathy. Four years ago, he noted bilateral lower extremity numbness below the knee, particularly in his shins. At the time he also had a right transcarpal ligament release at an outside institution for a diagnosis of carpal tunnel syndrome. This procedure did not provide any relief of his right-hand numbness. He also had numbness in his left hand. One year ago, he began tripping over his feet due to ankle weakness, resulting in falls on several occasions. Concurrently, he complained of burning in the hands more than in the feet, and treatment with gabapentin and a topical Lidoderm patch was started. Six months ago, he started having bilateral hand weakness with trouble opening jars or manipulating buttons. At the same time, he developed near-syncope and was found to have orthostatic hypotension, and treatment with midodrine was started. A Foley catheter was placed 1 year ago because of urinary retention and bilateral hydronephrosis, attributed at the time to benign prostatic hypertrophy. He also noted erectile dysfunction and constipation for a few years. The patient reported an involuntary 25-pound weight loss in the last year. His medical history included bilateral cataract surgery at 75 years but was otherwise negative. He denied any family history of neuropathy. He was a heavy smoker but did not drink or use illicit drugs. There were no toxic exposures. His general examination showed a drop of 20 mm Hg in his systolic blood pressure when standing without an increase in pulse rate. His mental status and cranial nerves were normal. His intrinsic hand muscles were atrophic. He had bilateral mild proximal and severe distal weakness in his arms and legs. He had loss of sensation to pinprick up to the knees and midforearms bilaterally …

A 48-year-old woman was referred to the neuromuscular clinic because of progressive generalized weakness for 4 months. Her symptoms started after she had a thyroidectomy and radioactive iodine treatment for a thyroid papillary carcinoma. She had proximal arm weakness when washing her hair and had trouble climbing steps and getting out of her chair without using her arms. About 2 months later, she developed fluctuating bilateral ptosis and blurred vision. Her symptoms were associated with episodes of transient horizontal binocular diplopia that would last for a couple of minutes and get worse by the end of the day. She also had dry eyes and mouth. A month later, she started having episodes of transient dysarthria. At that time she was found to have a low am cortisol level by the medical team while being evaluated for her symptoms. She was treated with a hydrocortisone taper which partially improved her weakness and a follow-up cortisol level suggested resolution of the adrenal insufficiency. The patient was on levothyroxine with normal thyroid gland function. She smoked 1 or 2 cigarettes daily for 10 years. She denied head drop, shortness of breath, lightheadedness, constipation, or weight loss. Her general examination, including orthostatic blood pressure, was normal. Her mental status was normal; visual acuity could be corrected to 20/20. Her pupils were symmetric with a sluggish response to light. Extraocular movements were intact and there was no ocular misalignment on alternate cover testing. There was no lid-twitch. She had mild right ptosis that worsened with sustained upgaze. Facial sensation was intact. There was no facial weakness, dysarthria, or dysphagia. The palate was midline and elevated symmetrically. The tongue movements were normal. No fasciculations were observed. Her strength was 4/5 in both biceps and psoas, which improved on repeated testing. The remaining neurologic examination, including deep …

A 32-year-old woman presenting with a rapidly progressive ALS-like syndrome was found to be HIV positive with a CD4 count of 44/mm(3). The patient recovered completely during 1 year after treatment with nelfinavir, zidovudine, and lamivudine, and recovery is sustained nearly 4 years later. Recovery was accompanied by HIV RNA becoming undetectable in plasma and CSF.

Reverse transcriptase has been detected in the serum of HIV-negative patients with amyotrophic lateral sclerosis (ALS). An ALS-like disorder in HIV-positive patients can remit with antiretroviral therapy. Using the product enhanced assay technique, we measured reverse transcriptase activity in the serum and CSF of 23 HIV-negative patients with ALS and 21 neurologic disease controls. Results for CSF were not significant, whereas reverse transcriptase was detected in 56% of ALS sera vs 19% of controls.

A 34-year-old, previously healthy woman presented with a 3-year history of persistent numbness and tingling in her feet ascending to the knees. She was a lifelong long-distance runner, and she normally experiences numbness and tingling in both feet while running that resolve within minutes of stopping her exercise. Three years ago, she developed diarrhea that was followed a week later by paresthesias in her feet and legs with a stocking distribution to the knees. Her symptoms were associated with a transient feeling of overwhelming fatigue, limiting her ambulation to 1 city block. She did not, however, have any functional weakness. After 2 weeks, milder hand and left face paresthesias developed. Four weeks later, her symptoms plateaued and persisted. Three months later, she developed more intense paresthesias and a sensation of “crawling” below both knees. At that time, she was seen at another hospital, where the examination showed bilateral pes cavus and hammertoes. There was no nerve thickening. Cranial nerves were intact. Strength was normal except for mild bilateral thenar weakness and slight difficulty with heel walking. The deep tendon reflexes were decreased at the arms and ankles. There was decreased pinprick sensation in the feet in a stocking-glove distribution with hyperalgesia. Vibration was moderately diminished at the ankles. Nerve conduction studies and electromyography (NCS/EMG) at that time showed uniform, mild conduction velocity slowing of both sensory and motor conduction with borderline prolonged distal latencies in the median and ulnar nerves. She was treated with a 1-month taper of prednisone beginning with 80 mg daily. The crawling sensation resolved and the paresthesias became less intense and stabilized. She was able to resume distance running, but still had persistent, mild numbness in her feet with bouts of increasing intensity every several months. Three years later, the patient presented to us for a …

We congratulate Sorenson et al.1 for their well-executed IGF-1 trial in patients with amyotrophic lateral sclerosis (ALS). While the title appropriately reflects the subcutaneous mode of IGF-1 delivery, the article fails to distinguish this critical limitation. What is the bioavailability in CSF and brain parenchyma in humans treated twice daily with 0.05 mg/kg IGF-1? Animal studies indicate that subcutaneous delivery of ∼0.8 mg/kg IGF-1 results in a maximal CSF concentration of 3 ng/mL IGF-1 at 2 hours postinjection.2 This equates to 0.4 nM IGF-1 in CSF at peak. The Sorenson et al. trial dose was 16-fold lower, suggesting that the maximal CSF concentration in patients would be 0.025 nM. The Kd of the IGF-1 receptor is 0.15 nM.3 Therefore, at 0.025 nM, only 14% of high-affinity and less than 1% of low-affinity receptors will be occupied. Likewise, the concentration of IGF-1 in CSF overestimates the bioavailable concentration within the brain parenchyma. IGF-1 injected into the lateral ventricle of rats exhibits a half-life of only 12 minutes in the CSF and penetrates …

Article abstract-We report limitation of gaze and slow saccadic eye movements by clinical examination and video-oculography in a patient with Becker muscular dystrophy. This rare association suggests that a dystrophinopathy should be considered in a patient with features characteristic of Becker muscular dystrophy even when mild impairment of eye movements is present. NEUROLOGY 1996;46: 564-566

Muscle dysfunction related to clozapine treatment is largely unrecognized. We evaluated weekly creatine kinase (CK) levels in 37 consecutive clozapine-treated outpatients with chronic psychotic disorders. Those with CK elevations underwent clinical neurologic evaluation, electromyography (EMG), and nerve conduction studies. Patients with probable myopathy had a quadriceps muscle biopsy. Twenty control patients had a single CK level determination. Twenty-nine of 37 clozapine-treated patients had CK elevations. Three patients had extreme CK elevations (> 20,000 IU/L), without myoglobinuria. Mean CK levels were significantly greater in clozapine patients (194 IU/L) than in control patients (142.3, p = 0.033). Of 18 clozapine-treated patients evaluated clinically, 6 had mild proximal weakness. EMG in 13 patients was myopathic in 5, normal in 5, and neurogenic in 3. Muscle biopsy in 5 patients showed rare regenerating myofibers and mild acute denervation (1), mild type II fiber atrophy (1), minimal acute denervation (1), and normal muscle (2). In conclusion, clozapine therapy may be associated with CK elevations and, rarely, mild myopathy.

Intravenous immunoglobulin (IVIg) is an effective and safe treatment for some patients with chronic inflammatory demyelinating polyneuropathy (CIDP). [1-4] Some patients who initially responded to IVIg infusion may subsequently deteriorate clinically, become refractory to increasing IVIg dosages, and require treatment with more toxic immunosuppressive agents. The reasons why IVIg becomes ineffective are unclear, but may involve an inability to ``keep up'' with autoantibody production. We describe a patient with CIDP who, despite an impressive initial response to IVIg, became refractory to progressively higher dosages. A short course of plasma exchange (PE) restored longterm IVIg efficacy. A 57-year-old man presented with 3 months of progressive numbness of the legs and arms, facial numbness, left arm and leg weakness, and prominent fatigue. He had previously been diagnosed with CIDP, based on clinical and electrophysiologic results, and had been on prednisone (60 mg/d) and azathioprine (150 mg/d) for the preceding 3 months without improvement. Neurologic examination demonstrated marked hypesthesia in the mental nerve distribution bilaterally. Strength was 4/5 in proximal arm muscles and 4-/5 in forearm and intrinsic hand muscles. Right leg strength was 5-/5 throughout, and left leg strength was 4/5 proximally and 4-/5 distally. The patient was unable to walk on …

Objective: To study the effect of vitamin D (VitD) supplementation on the ALSFRS (Amyotrophic Lateral Sclerosis Functional Rating Scale) in ALS patients. Background ALS patients commonly have low vitD levels. It is not known whether vitD supplementation has an effect on the ALSFRS. Design/Methods: ALSFRS changes in 20 patients with ALS who took 2000IU of vitD daily were compared to 17 patients who didn9t take vitD over 12 months. ALSFRS changes 9 months prior to vitD supplementation were also compared to ensure that the two groups had similar progression prior to starting vitD. Patients were examined every 3 months. Follow-up vitD was obtained 6 months after starting supplementation. Results: ALSFRS decline was slower in patients who took vitD at 3, 6 and 9 months (p=0.04, 0.03 and 0.009 respectively). At 12 months the change in ALSFRS was similar in the 2 groups but follow-up was available for only 6 vitD patients and 7 nonvitD patients (p=0.77). Over 9 months prior to starting vitamin D, the two groups had a similar change in ALSFRS. Other demographics such as age, time since disease onset, vitamin D levels, use of Bipap, Peg tube, FTD, weight loss, ALSFRS at baseline, use of riluzole, depression, smoking and number of patients who died during the study was similar in the 2 groups. Follow-up median vitD levels rose from 18.5 to 31.0 ng/mL at 6 months in the group taking vitD. No side effects secondary to vitD supplementation were reported. Conclusions: VitD supplementation at 2000 IU daily reduced the ALSFRS decline in ALS patients at 3, 6 and 9 months. This effect was lost at 12 months but the number of patients followed at 12 months was small. A larger number of patients is needed to determine whether the beneficial effect of vitD persists after 12 months of supplementation. Disclosure: Dr. Karam has received personal compensation in an editorial capacity for Neurology Resident & Fellow Section. Dr. Barrett has nothing to disclose. Dr. Altememi has nothing to disclose. Dr. Imperato has nothing to disclose. Dr. MacGowan has nothing to disclose. Dr. Scelsa has received personal compensation for activities with Avanir Pharmaceuticals and GlaxoSmithKline. Dr. Scelsa has received personal compensation in an editorial capacity for Peripheral Neuropathies in Clinical Practice. Dr. Scelsa has received research support from the NIH.