Melvin Greer

Multiple sclerosis risk after optic neuritis: Final optic neuritis treatment trial follow-up

OBJECTIVE To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk. DESIGN Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006. SETTING Neurologic and ophthalmologic examinations at 13 clinical sites. PARTICIPANTS Three hundred eighty-nine subjects with acute optic neuritis. MAIN OUTCOME MEASURES Development of MS and neurologic disability assessment. RESULTS The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44%-56%) and strongly related to presence of lesions on a baseline non-contrast-enhanced magnetic resonance imaging (MRI) of the brain. Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, optic disc swelling, and certain atypical features of optic neuritis. CONCLUSIONS The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS. In the absence of MRI-detected lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis.

Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children

OBJECTIVE. Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS. Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME. There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor δ-aminolevulinate. CONCLUSIONS. In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Stereotactic pallidotomy lengthens the transcranial magnetic cortical stimulation silent period in Parkinson's disease

We compared the duration of the EMG cortical stimulation silent period(CSSP) elicited in abductor pollicis brevis using transcranial magnetic stimulation (TMS) before and after stereotactic unilateral globus pallidus internus pallidotomy (PAL) in 12 patients with Parkinsons disease. We used TMS stimulus intensities of 200, 150, 120, and 100% of motor evoked potential(MEP) threshold before and after (86 ± 25 days) PAL. PAL increased CSSP duration at stimulus intensities of 200% of MEP threshold in the hand contralateral to the stereotactic lesion. In a subset of five patients able to remain at rest during pre-PAL testing sessions, PAL decreased the resting MEP/M-wave area ratio in the hand contralateral to the lesion at a stimulus intensity of 120% of MEP threshold. PAL did not significantly modify the effects of TMS in the hand ipsilateral to the globus pallidus lesion. The results suggest that PAL improves the function of cortical motor inhibitory circuits in Parkinsons disease.

BENIGN INTRACRANIAL HYPERTENSION. VI. OBESITY.

THE HIGH INCIDENCE of obesity in women suffering from the neurological syndrome benign intracranial hypertensions2 infers a relationship that may be based on endocrine changes which coexist. This interpretation is supported by the frequently seen alterations in menstrual function in obesity3 and impressions derived from the study of this syndrome in females who appeared to be undergoing a state of hormonal imbalance: pregnancy,4 menarche,5 and menstrual dysfbnction.O Clinical study. This study describes the course of 20 obese females who were admitted to the Columbia-Presbyterian Medical Center and the University of Florida Teaching Hospital because of unlocalized increased intracranial pressure, which was unassociated with focal signs of neural impairment, convulsions, mental dysfunction, or cerebrospinal fluid changes. Five were seen personally. Fourteen were Caucasian, and 6 were Negro (see chart). All patients were considered obese on the basis of clinical impression and when compared with standard charts. None were hypertensive, pregnant, or overtly edematous. Although 5 patients acknowledged a recent weight gain (10 to 30 Ib. within six months), 9 others stated their weight was relatively stable during the past year. Irregularities of menstrual function including amenorrhea, intermenstrual bleeding, and prolonged menstruation occurred intermittently in 6 patients. These signs of menstrual dysfunction were not related temporally to recent weight gain or the signs and symptoms of intracranial hypertepsion. Neurological symptoms and signs. Symptoms suggesting increased intracranial pressure were described by all patients for periods of one to ten months. Initially the symptoms were inter-

Benign intracranial hypertension: IV. Meriarche

BENIGN INTRACRANIAL HYPERTENSION has been recognized more frequently in females than and for this reason ovarian hormones and their interaction with other endocrine systems have been implicated as possible etiological factors.* The evidence has been indirect, however. The theory was advanced that an anticipated increased production of estrogen and its suppressive effect upon the adrenal cortex was responsible for the syndrome in pregnant women who suffered from benign intracranial hypertension.4 Another group of females with the syndrome in whom hormonal change is occurring are those who have entered puberty and who have recently experienced the onset of menstruation (menarche) or in whom the presence of secondary sex characteristics indicates the imminence of menarche.

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinsons disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.

Transport of intrathecal 131I RISA in benign intracranial hypertension

SUMMARYThree patients with benign intracranial hypertension were studied with the techniques of RISA isotope cisternography and absorption. Two of 3 patients had a decreased plasma absorption of intrathecally injected 131I RISA at twenty-four hours. These findings suggest that in some cases of benign intracranial hypertension the increased intracranial pressure reflects an abnormality of CSF absorption through the arachnoid villi.

Determination of urinary 3-methoxytyramine, normetanephrine and metanephrine in pheochromocytoma and neuroblastoma by gas chromatography☆

Abstract A gas chromatographic method for the determination of 3-methoxytyramine, metanephrine and normetanephrine has been developed and applied to their determination in the urine of patients with neuroblastoma and pheochromocytoma.

Emotional conversations in Parkinson’s disease

Objective: To learn how PD influences verbal description of emotional events. Background: Individuals with PD exhibit emotional processing deficits. Emotional experience likely involves several dimensions (e.g., valence, arousal, motor activation) subserved by a distributed modular network involving cortical, limbic, basal ganglia, diencephalic, and mesencephalic regions. Although the neurodegeneration in PD likely affects components in this network, little is known about how PD influences emotional processing. Because PD is associated with activation deficits, one could predict that the discourse of emotional experiences involving high activation would be reduced in patients with PD compared to control subjects. Alternatively, because patients with PD exhibit paradoxical sensitivity to externally evoked motor activation (kinesia paradoxica), it is possible that emotional stimuli may facilitate verbal emotional expression more so in patients with PD than in control subjects. Methods: The authors measured verbal descriptions of personal emotional experiences in subjects with PD and normal controls. Results: Compared with control subjects, individuals with PD showed a relative increase in the number of words spoken and in discourse duration when talking about emotional experiences that are usually associated with high levels of arousal and motor activation. Although the authors did not measure arousal or activation, prior research has shown that, when asked to recall an emotional experience, people will often re-experience the emotion previously experienced during that episode. Conclusions: Recalling emotional episodes induces verbal kinesia paradoxica in patients with PD. Although recall of these emotional episodes may have been associated with increased arousal and activation, the mechanism underlying emotional verbal kinesia paradoxica is unclear.

Gas chromatography of urinary vanilmandelic acid in pheochromocytoma

Abstract The properties and suitability of six different volatile derivatives of 3-methoxy-4-hydroxymandelic acid (VMA) were established on a non-polar and three polar columns, and the optimum conditions for determination of VMA by gas chromatography were established for a patient with pheochromocytoma. The method was then applied to eight other patients with pheochromocytoma. In all patients, VMA was significantly elevated. The advantages and disadvantages of the method are compared briefly with other methods reported in the literature.