BACKGROUND: It has been known for decades that monoclonal IgM gammopathies are associated with peripheral neuropathies. However, available data are from ultraspecialized laboratories, while little is ...reported about their epidemiology. PATIENTS AND mETHODS: Since 1988 we have recorded a registry of the patients referred for a peripheral neuropathy. Database included clinical, electrophysiological, laboratory, immunological and pathological data. All the patients were followed‐up with clinical visits or at least phone interview every six months. In case of death we evaluated death certificates and contacted general practitioners. Results: In the period from 1988–1999 we saw and followed‐up 512 patients with clinical ascertained peripheral neuropathy. Of those patients, 35 (6.8%) had a MGUS: 18 IgG, 10 IgM, and 7 IgA. The patients with IgM paraprotein were all men, except 1 woman, aged 48 to 71 years at the onset of symptoms. Eight patients had a predominantly sensitive neuropathy and two patients a motor neuropathy. Of the 8 patients with sensitive neuropathy, 3 had a demyelinating disease and antiMAG antibodies, 4 an axonal disease and antisulphatide antibodies, and 1 an axonal neuropathy with both antiMAG and antisulphatide antibodies. The two patients with motor neuropathy had both an axonal disease and anti‐GM1 antibodies. The patients with sensory neuropathy were treated with periodic plasmaphoresis plus i.v. cyclophosphamide every 4–6 months. The patients with motor neuropathy were treated every month with i.v. immunoglobulins alternated with i.v. cyclophosphamide. Follow‐up of those patients lasted 12 to 108 months. Four patients died: 3 with antisulfatide antibodies because of a developing cancer (2 a primary hepatic cancer and 1 a bladder neoplasm) and 1 with anti‐GM1 antibodies for respiratory failure. The remaining patients showed a slowly progressive invalidating disease especially with the loss of hand ability. Conclusions: The patients with monoclonal IgM gammopathy are a minority among those observed because of a peripheral neuropathy in a General Hospital. Prognosis is severe either because of growing dependency or of life shortening (directly or for developing cancer). Aggressive therapies probably deserve multicentric studies.
We report a case of acute rhabdomyolysis associated with acute intravenous cocaine intoxication in an asymptomatic HIV-positive young man and discuss the possible pathogenetic mechanisms. Recent ...cocaine use must be considered among the causes of acute rhabdomyolysis without obvious precipitating factors in our country too. The characteristically uncollaborative attitude of habitual drug users may make differential diagnosis very difficult to establish.
OBJECTIVES--To report experience of intra-arterial thrombolysis for acute stroke, performed with a microcatheter navigated into the intracranial circulation to impale the clot. METHODS--Patients were ...selected on the following criteria: (1) clinical examination suggesting a large vessel occlusion in stroke patients between 18 and 75 years; (2) no radiographic signs of large actual ischaemia on CT at admission; (3) angiographically documented occlusion of the middle cerebral artery (MCA) stem or of the basilar artery (BA), without occlusion of the ipsilateral extracranial internal carotid artery or of both the vertebral arteries; (4) end of the entire procedure within six hours of stroke. 12 patients with acute stroke were recruited, eight of whom had occlusion of the MCA stem and four of the BA. Urokinase was used as the thrombolytic agent. RESULTS--Complete recanalisation in six MCA stem and in two BA occurred, and partial recanalisation in two MCA stem and one BA. There was no recanalisation in one BA. A clinically silent haemorrhage occurred in two patients, and a parenchymal haematoma in one patient, all in MCA occlusions. At four months five patients achieved self sufficiency (four with MCA and one with BA occlusion). Six patients were dependent (three totally), and one died. CONCLUSIONS--The strict criteria of eligibility allowing the enrollment of very few patients and the procedure itself, requiring particular neuroradiological expertise, make this procedure not routine. Nevertheless, the approach can be considered a possible option for patients with acute ischaemic stroke.
Parasympathetic function in 7 Huntington's chorea patients with a duration of the disease ranging from 1 to 20 years, was evaluated by studying R-R intervals during quiet and deep breathing and ...Valsalva manoeuvre. All 7 patients were free of neuropathy, orthostatic hypotension, heart or lung disease and had had no medication for at least 15 days prior to hospitalization. Seven normal subjects served as controls. On the whole, the responses of the Huntington's chorea patients were not significantly different from those of the controls. Abnormal responses to all the tests were received in only one patient and a low R-R variability during deep breathing in the youngest patients. Unlike other Central Nervous System degenerative disorders, in Huntington's disease parasympathetic autonomy seems to be sufficiently preserved.
Objective
To assess the safety, tolerability, pharmacodynamics, and preliminary efficacy of eptastigmine, a new long‐acting cholinesterase inhibitor, in patients with probable Alzheimer's disease.
...Methods
This was a double‐blind, randomized, placebo‐controlled, unbalanced parallel‐group study. One‐hundred and three patients (83 in the eptastigmine group and 20 in the placebo group) were recruited by 10 centers. Patients received 20 mg eptastigmine or placebo for 4 weeks with twice‐a‐day or three‐times‐a‐day regimens, depending on body weight (≤65 kg or >65 kg, respectively). Patient performance on the Logical Memory Test, Semantic Word Fluency Test, Trail Making Test, Index of Independence in Activities of Daily Living, Instrumental Activities of Daily Living Scales (IADL), and the Physician and Caregiver Clinical Global Impression of Change (CGIC) was assessed at baseline and at the end of treatment.
Results
Nine patients, all from the eptastigmine group, did not complete treatment because of uncooperativeness (n = 3), adverse events (n = 3), protocol violations (n = 2), and clinical decline (n = 1). Twenty‐five patients receiving eptastigmine (34%) reported adverse events mainly of the cholinergic type. Cholinergic side effects were generally associated with peak red blood cell cholinesterase inhibition exceeding 50% after the first dose, or 70% at steady state. At steady state, average daily acetylcholinesterase inhibition ranged from 13% to 54%. Overall, 34% of patients receiving eptastigmine versus 0% receiving placebo (p = 0.006) improved on the Physician CGIC. This percentage increased to 46% in the subgroup of patients with average daily acetylcholinesterase inhibition ranging from 30% to 35%. Patient performance on the IADL also improved significantly compared with the placebo group (p = 0.019). In the eptastigmine group, performances on all tests and scales improved with an inverted U‐shaped relation to average daily acetylcholinesterase inhibition.
Conclusions
This study shows that doses of 40 to 60 mg per day of eptastigmine are relatively safe and well tolerated and that moderate acetylcholinesterase inhibition is associated with maximal cognitive efficacy.
Clinical Pharmacology & Therapeutics (1996) 60, 218–228; doi:
There is little evidence of autonomic dysfunction in PD, although autonomic disturbance was included in the original description by J. Parkinson. In addition, there are no data for de novo PD ...patients. We selected 14 de novo parkinsonians (seven men and seven women), aged 62.7 +/- 8.2 years, with mild disease (stage 1 through 2 on the Hoehn and Yahr's scale), without history of diabetes, heart disease, or alcoholism, and without neuropathy or orthostatic hypotension. Fourteen age- and sex-matched normal persons were controls. We found a highly significant difference in the respiratory sinus arrhythmias during deep breathing (p less than 0.01); the basal heart rate, the respiratory sinus arrhythmias during quiet breathing, and the Valsalva ratios did not differ statistically, however. In the absence of neuropathy and orthostatic hypotension and in the presence of normal Valsalva ratios, we believe that the abnormality found by us may apply only to parasympathetic dysfunction, perhaps at a central level. In addition, the abnormality seems to be independent of stage and therapy.
The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic ...supratentorial stroke.
Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months.
Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences.
These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke.
A case of HMN, distal type transmitted as autosomal dominant is described. Clinical findings appear to be consistent with a peroneal muscular atrophy, indistinguishable from HMSN types I and II. The ...electrophysiological data reveal a pathological involvement of the anterior horns, whereas sensory and motor conduction are normal. A muscle biopsy showed neurogenic atrophy, while the morphology of the sural nerve was normal.
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