Multiple sclerosis treatment 2001.

Trials of new MS drugs now require MR imaging and clinical data and entail enormous expense. Therefore, science can ask and answer only a limited number of questions, so physicians must use their clinical acumen to judge (or conjecture) the best treatments for their patients. The drugs discussed earlier will dominate MS therapy in the next few years, but further advances may come from one of the more than forty new agents now under investigation for alleviating MS. It is an exciting time for patients and their doctors.

Migraine versus multiple sclerosis.

A headache associated with focal neurological signs and symptoms is always a clinical dilemma.

Cerebrospinal fluid in acute optic neuritis: experience of the optic neuritis treatment trial.

The Optic Neuritis Treatment Trial (ONTT) is a prospective study of corticosteroid treatment of acute optic neuritis (ON), with subsequent longitudinal follow-up to determine development of clinically definite multiple sclerosis (CDMS). We analyzed the CSF of 83 patients with clinically isolated ON who underwent lumbar puncture within 24 hours of enrollment into the ONTT to determine the value of CSF changes in ON, especially regarding diagnostic utility, immunologic changes, MRI correlations, and progression to CDMS. All patients had baseline MRI scans graded for changes typical of MS. CSF measurements included immunoglobulin G (IgG) synthesis, IgG ratio, myelin basic protein, IgG kappa light chains, and oligoclonal banding. No patients had their diagnosis or management altered as a result of CSF findings. Except for oligoclonal bands, few patients showed any abnormalities on CSF tests, and no tests correlated with the 2-year development of CDMS. Oligoclonal banding, present at baseline in 11 of 13 patients who developed CDMS, did predict progression to CDMS, but this was not independent of MRI abnormalities. Two patients with oligoclonal bands and a normal MRI did progress to CDMS. We conclude that CSF analysis may not be necessary in the routine evaluation of patients presenting with a typical clinical profile of acute ON, and that most CSF tests add little additional information to MRI results for predicting the 2-year development of CDMS. However, the precise role of oligoclonal banding in the analysis of such patients awaits longer follow-up of this cohort.

The diagnosis of multiple sclerosis.

The process of diagnosing multiple sclerosis (MS) is much like that of analyzing evidence in a courtroom; they both rely on reason, judgement, and experience, rather than on any formal set of diagnostic criteria. The history, physical examination, and laboratory tests all have limitations and pitfalls that make MS one of the most difficult diseases to diagnose.

Clinical features of Todd's post-epileptic paralysis.

Two hundred and twenty nine patients with generalised tonic-clonic seizures were prospectively evaluated. Fourteen were identified who had transient focal neurological deficits thought to be Todd's post-epileptic paralysis (PEP). Eight of these 14 patients had underlying focal brain lesions associated with the postictal deficits. All patients with PEP were weak, but there was wide variation in the pattern (any combination of face, arm, leg), severity (plegia to mild), tone (spastic, flaccid, or normal), and reflexes (increased, decreased, or normal). Significant sensory loss occurred in only one patient. The only other signs of PEP were aphasia (in five patients all with underlying lesions) and gaze palsy (in four patients). Post-epileptic paralysis persisted from half an hour to 36 hours (mean of 15 hours). Post-epileptic paralysis may occur with the first seizure or after many years of seizures and does not appear after every seizure. The clinical features of PEP are thus heterogeneous.

Literary neurologic syndromes. Alice in Wonderland.

Many neurologic syndromes are named for literary characters. For example, the "Alice in Wonderland" syndrome of altered body perceptions, usually caused by migrainous ischemia, is so called because of the resemblance of its symptoms to the fluctuations in size and shape that plague the main character in Lewis Carroll's 1865 novel Alice in Wonderland. The medical symptoms of distorted body images match the literary description so precisely that illustrations from the original book depict them very accurately. Because Lewis Carroll suffered from classic migraine headaches, scholars have speculated that he may have experienced this syndrome himself.

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis.

We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant.

Headaches and multiple sclerosis: a clinical study and review of the literature.

Whether multiple sclerosis (MS) can cause headaches is controversial. To clarify the association between headaches and MS we prospectively analyzed 104 consecutive MS patients using detailed headache evaluations. Fifty-four patients (52%) reported headaches, compared with 5 of 35 (14%) patients initially suspected to have MS but subsequently proven to have other disorders, and 18 of 100 (18%) matched general neurology patients. The MS patients had tension headaches or vascular headaches of the migraine type; there was no distinctive "MS headache." Seven of these patients had headaches with their first MS symptoms, but in only one did headaches recur with disease activity. Headaches did not correlate with any clinical features of MS. We conclude that an association between headaches and MS may exist.

Low yield in the diagnostic evaluation of transient ischemic attacks.

Among 163 patients presenting with the clinical features of a TIA, extensive testing identified only 2 patients with nonatherosclerotic causes. We conclude that most patients with a TIA have atherosclerotic vascular disease and that screening tests for other etiologies have a low yield.

Psychogenic sensory loss.

One hundred consecutive patients complaining of hemifacial numbness were tested for two features commonly thought to indicate psychogenic sensory loss: a) exact splitting of the midline to pinprick, and b) diminished vibratory sensation on the affected forehead. Twenty patients had purely psychogenic complaints, while 80 had organic lesions. Sensory loss split the midline in four patients (20%) with psychogenic complaints but also in six patients (7.5%) with structural lesions (p = NS). Vibration was diminished in 19 patients (95%) with psychiatric disease but also in 69 patients (86%) with organic lesions (p = NS). Contrary to popular beliefs, these "nonphysiologic" findings do not distinguish psychogenic from organic sensory loss.

Arteriovenous malformation presenting as hemidystonia.

Two men, aged 25 and 33 years, had progressive hemidystonia and an arteriovenous malformation (AVM) in the contralateral cerebral hemisphere. One patient with an AVM in the posterior basal ganglia of the right hemisphere had an older brother with severe generalized dystonia. The second patient had an AVM in the left cortical and subcortical parietal area with no obvious lesion in the basal ganglia. Unlike generalized dystonia, a focal lesion is commonly found in patients with unilateral dystonia. The association of AVM-induced hemidystonia and family history of dystonia suggests that genetic predisposition may be important in some patients with hemidystonia.

Silent myocardial infarction and diabetic cardiovascular autonomic neuropathy.

Seventy-three consecutive diabetic adults with symptomatic peripheral neuropathy were evaluated for the presence of cardiovascular autonomic neuropathy and electrocardiographic evidence of myocardial infarction (MI). Twenty-five (34.2%) patients demonstrated cardiovascular autonomic neuropathy, and ten (13.7%) patients had electrocardiographic evidence of MI. Of the ten MI identified, seven were asymptomatic (silent) by history. The incidence of silent MI was significantly higher (P less than .04) in patients with cardiovascular autonomic neuropathy. It is postulated that sudden death in diabetic patients with cardiovascular autonomic neuropathy may be due to silent MI.