Serial evoked potential studies and MRI imaging in chronic progressive multiple sclerosis.

Measurements of serial evoked potential latencies and plaque burden on MRI scans are often obtained during clinical studies of multiple sclerosis patients to provide additional information to the disability-based primary endpoints. The ideal laboratory-based marker of progression would be expected to significantly change over the time period of study. Serial visual (VEP) and brainstem auditory evoked potentials (BAEP) and MRI scans of 11 chronic progressive MS patients were obtained over a 1.5 year period in a clinical study. Over this period, there was no significant change in disability as measured by the Kurtzke EDSS, Ambulation Index or Neurological Rating Score. The VEP P100 significantly progressed over the period of study. However, the MRI T(2) plaque burden and BAEP I-V intrapeak latency did not significantly progress over the 1.5 years. We conclude that, in chronic progressive MS, serial visual evoked potential tests may complement standard disability-based endpoints to assess disease progression.

A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis.

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS.

Frequency of magnetic resonance imaging abnormalities in patients with migraine.

BACKGROUND: The frequency of magnetic resonance imaging (MRI) abnormalities in patients with migraine has been reported at 12% to 46%. We examined a series of patients to determine the frequency of MRI abnormalities, and any relationship of frequency with patient age, sex, migraine type, duration of symptoms, and other medical conditions. METHODS: Magnetic resonance imaging findings were reviewed retrospectively with respect to presence of focal white matter hyperintensities in 185 consecutive patients. Patients had been diagnosed with migraine by a neurologist. All images had been interpreted by a neuroradiologist. Clinical information was obtained by chart review. RESULTS: Sixteen percent had focal white matter abnormalities. Among patients less than 50 years old, and without other medical problems such as hypertension, atherosclerotic heart disease, diabetes mellitus, autoimmune disorder or demyelinating disease, only 6% had white matter abnormalities. Increased frequency of white matter abnormalities was associated with age and medical risk factors, but not with sex, migraine subtype, or duration of migraine symptoms. CONCLUSION: The observed frequency of MRI abnormalities in our series is lower than has been previously reported. In many cases, these abnormalities may be unrelated to migraine. When such changes are discovered in a patient with migraine, other etiologies should be considered.

Relationship of 133Xe cerebral blood flow to middle cerebral arterial flow velocity in men at rest.

Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

Spontaneous intracranial hypotension: headache with a reversible Arnold-Chiari malformation.

Spontaneous intracranial hypotension is characterized by severe postural headache in the setting of low CSF pressure, usually attributed to a cryptic CSF leak. We report a patient whose prolonged refractory headache was characterized by the clinical symptoms of occipital neuralgia, but was also associated with the radiographic appearance of an Arnold-Chiari malformation, type I and low CSF pressure. After extensive diagnostic evaluation, CT cisternomyelography ultimately demonstrated a CSF leak at the C2 vertebral level. Symptomatic relief was sustained only with long-term theophylline administration. The apparent Arnold-Chiari malformation resolved with treatment of the low CSF pressure.

A longitudinal study of the T cell activation marker CD26 in chronic progressive multiple sclerosis.

Activated T cells are implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Serial measurements of T cell activation molecules and T cell subpopulations were performed over 12 months in patients with chronic progressive multiple sclerosis and healthy controls, and correlated with clinical indices of disease progression measured by standardized disability scores. Of the markers studied, the activation molecule CD26 appeared to exhibit a more consistent pattern and to be elevated in MS patients; therefore we concentrated our attention on this marker, especially in view of recent evidence of its role in T cell activation. In this small patient group, the elevation of CD26 in the MS patients did not reach statistical significance, when compared to the level in the controls. Interestingly, the percentage of CD26 but not CD25 or HLA-DR correlated with the MS patients' disability scores. However, the clinical significance of this observation as an indication of disease activity in chronic progressive MS remains to be demonstrated in studies of larger patient populations.