Surgical therapy for multiple sclerosis tremor: a 12-year follow-up study.

BACKGROUND AND PURPOSE: Severe multiple sclerosis (MS) tremor causes disability poorly responsive to medication. Deep brain stimulation (DBS) or thalamotomy can suppress tremor, but long-term outcomes are unclear. METHODS: Nine patients with MS tremor underwent disability measures at baseline and 12 months post-surgery (six thalamotomy, three DBS) in 1997-1998 (previously reported, Matsumoto et al., Neurology 2001;57:1876-82). We report the prospective 12-year follow-up of this cohort for tremor, disability, and death. RESULTS: Surgery was initially successful in all. Tremor recurred in all patients within median 3 months, although two DBS patients were tremor-free for 5 years. Median tremor-free survival (tremor-free time/survival time) was 4.3%. At 12-year follow-up, four survivors (two thalamotomy, two DBS) (Expanded Disability Status Scale scores 8-8.5) were severely disabled. Five patients were dead (four thalamotomy, one DBS) median 5.8 years post-operative. CONCLUSIONS: Surgery benefit for severe tremor was overall short-lived (median 3 months), with long-term poor prognosis. Although two DBS patients had sustained 5-year tremor-suppression, the observed progressive disability and death in this cohort bear importance for long-term success in future MS tremor surgery trials.

Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

BACKGROUND: Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. OBJECTIVE: To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. METHODS: The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. RESULTS: All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. CONCLUSIONS: Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.

Parkinson's disease: medical and surgical treatment.

It has been over three decades since the introduction of L-dihydroxyphenylalanine or levodopa therapy for Parkinson's disease (PD). The early levodopa trials were driven by recognition of a profound cerebral dopamine deficiency state in this disorder. Whereas dopamine fails to cross the blood brain barrier and hence is ineffective as therapy, the amino acid precursor, dopa, is transported across this barrier and provides a substrate for dopamine synthesis. Levodopa is converted to dopamine within the brain by dopa decarboxylase, replenishing central dopamine stores and potentially reversing the motor symptoms of PD.

Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study.

OBJECTIVE: To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. METHODS: The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. RESULTS: For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age <72 years and to men. The OR for cigarette smoking was 0.69 (95% CI = 0.45 to 1.08, p = 0.1). The authors found no association between PD and alcohol consumption. Extreme or unusual behaviors such as tobacco chewing or snuff use and a diagnosis of alcoholism were significantly more common in control subjects than cases. CONCLUSIONS: These findings suggest an inverse association between coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor.

Eight patients with medically refractory disabling essential tremor underwent ventralis lateralis (VL) thalamotomies; the procedure was unilateral in seven cases and bilateral (staged) in the other. Contralateral tremor remained absent or markedly reduced in all patients at the time of the most recent follow-up examinations, at a mean of 17.3 months after surgery. Disability was determined by a modified form of an established rating scale for tremor, and was reduced from a mean score of 21.1 (moderate grade) to 3.9 (absent grade) (p less than 0.001). Interestingly, voice tremor was abolished or significantly improved in 71.4% of patients with preoperative voice tremor. This feature has not been reported previously. Persistent surgical morbidity was limited to two patients with mild dysarthria and one with a mild cognitive impairment. There were no surgically related deaths. It is concluded that stereotactic VL thalamotomy is a treatment option for medically intractable disabling essential tremor.

Stereotactic ventrolateralis thalamotomy for medically refractory tremor in post-levodopa era Parkinson's disease patients.

Thirty-six patients with Parkinson's disease and medically refractory tremor underwent stereotactic ventrolateralis thalamotomy at the Mayo Clinic between 1984 and 1989. All patients had been or were being treated with carbidopa/levodopa but with unsatisfactory tremor control. Modern stereotactic techniques, including microelectrode recording, were used to treat 36 patients, of whom 31 (86%) had complete abolition of tremor and three patients (5%) had significant improvement. Tremor recurred in two patients within 3 months of surgery; however, the remaining patients suffered no recurrence of tremor during follow-up periods ranging from 14 to 68 months (mean 33 months). Persistent complications (arm dyspraxia, dysarthria, dysphasia, or abulia) were noted in five patients but were a source of disability in only two. It is concluded that thalamotomy in carefully selected patients is a beneficial operation for the control of medically refractory parkinsonian resting tremor.

Parkinson's disease: new treatment strategies.

Recent interest has focused on two novel approaches to the treatment of Parkinson's disease-medications to slow or arrest disease progression, and cerebral transplantation. Two recent studies have demonstrated that selegiline can slow, although not halt, the progression of recent-onset Parkinson's disease. The data are sufficiently compelling to justify the use of this drug in most new patients. It also seems reasonable to extrapolate from the data and offer this medication to all patients but those with the most advanced Parkinson's disease. The current focus on excessive oxidative stress as a causative factor has led some investigators to recommended treating patients with the antioxidant tocopherol (vitamin E). There is no clinical evidence demonstrating its effectiveness, but a current multicenter study is being conducted, with the results expected within the next 2 years. High-dose vitamin E (such as 800 to 2000 U/d), taken for a number of months, is probably harmless. It is probably reasonable, therefore, to allow patients to take this over-the-counter compound until more definitive evidence is available. Another antioxidant, vitamin C, has also been advocated as a means of slowing the progression of Parkinson's disease. There are no studies that demonstrate any clinical effectiveness, and there are also no ongoing studies investigating this issue in patients with Parkinson's disease. The excitement surrounding the initially favorable results of adrenal-brain transplantation has waned with the failure of numerous institutions to replicate the original dramatic success. While mild or occasionally moderate improvement has been noted in subsequent patients undergoing adrenal-brain transplantation, the improvement has not been sufficient to justify the risk and expense of this surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-assisted stereotactic ventralis lateralis thalamotomy with microelectrode recording control in patients with Parkinson's disease.

Stereotactic ventralis lateralis thalamotomy can be performed in selected patients with medically intractable parkinsonian tremor and rigidity. New technology, including computed tomography-based stereotaxis and microelectrode recording techniques, provides a data base for precise localization of thalamic lesions tailored to each patient and thus reduces the risk associated with such a procedure. At our institution, 12 patients with medically intractable parkinsonian tremor have undergone this procedure; all experienced alleviation or cessation of the tremor and no permanent disabling neurologic sequelae.

Overeating and obesity from damage to a noradrenergic system in the brain.

A discrete, ascending fiber system that supplies the hypothalamus with most of its noradrenergic terminals was destroyed at midbrain level, both electrolytically and with local injections of 6-hydroxydopamine, a destructive agent specific for catecholaminergic neurons. The result was hyperphagia leading to obesity. Fluorescence histochemical analysis showed that loss of noradrenergic terminals in ventral bundle termination areas such as the hypothalamus was necessary for hyperphagia. Damage to dorsal bundle or dopaminergic projections was not. Prior treatment with desmethylimipramine to selectively block uptake of 6-hydroxydopamine into noradrenergic neurons prevented both hyperphagia and loss of norepinephrine fluorescence. The lesions that produced hyperphagia also reduced the potency of d-amphetamine as an appetite suppressant. It is concluded that this noradrenergic bundle normally mediates suppression of feeding, thereby influences body weight, and serves as a substrate for d-amphetamine-induced loss of appetite.