Faculty Bibliography

We studied the clinical (10 patients) and pathological (9 patients) findings in 13 patients with herpes zoster myelitis, all of whom had systemic illnesses associated with immunosuppression. The median interval between the onset of the herpes zoster rash and myelopathic symptoms was 12 days, and the subsequent median interval to maximal deficit was 10.5 days. Presenting neurological symptoms were characteristically ipsilateral to the rash, with motor dysfunction predominating, followed by a spinothalamic and, less often, posterior column sensory deficit. Pathological involvement was most severe in the dorsal root entry zone and posterior horn of the spinal cord segment corresponding to the involved dermatome. There was variable spread both horizontally and vertically in the spinal cord. Direct varicella-zoster virus (VZV) infection of neuroectodermal cells, particularly oligodendrocytes, was demonstrated by immunostaining viral antigens (8 cases), and by the presence of Cowdry type A intranuclear inclusions (7 cases) and often was associated with focal demyelination (6 cases). In 4 patients a VZV vasculitis was associated with leptomeningitis and haemorrhagic necrosis (spinal cord in 1; brainstem or cerebellum in 3). The protracted evolution in many cases and the pathologically documented direct viral infection of the spinal cord provide a rational basis for the use of antiviral therapy in preventing or attenuating the evolving myelopathy

We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM

Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical evaluation in the United States. During a controlled clinical trial conducted at the National Institutes of Health Clinical Center, FBM was added to constant carbamazepine (CBZ) monotherapy. CBZ total concentrations were reduced during active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001). The effect was evident after the first week of treatment and reached a plateau in 2-4 weeks. To clarify the interaction mechanism, free and total concentrations of CBZ and its plasma metabolites were determined by high-performance liquid chromatography (HPLC) and ultrafiltration in four patients. In these patients, FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E) concentrations (p less than 0.01). Free fractions of all compounds were unmodified. FBM appears to be capable of inducing CBZ metabolism. CBZ-FBM interaction may be clinically relevant

We studied 40 patients with temporal lobe epilepsy to determine if ictal fear was associated with changes in cognition, personality, or psychopathology. Patients with ictal fear scored higher (p < 0.10) than those without ictal fear on the Minnesota Multiphasic Personality Inventory (MMPI) Social Introversion and Psychasthenia subscales, MMPI-derived scales including depression, poor morale, and delinquency and on the Spielberger Trait Anxiety Scale. These differences were not even marginally significant with Bonferoni correction for multiple comparisons. No differences were found between these groups in the Temporal Lobe (Bear-Fedio) Questionnaire, Buss-Durkey Hostility Inventory, or history of psychiatric hospitalization. However, a history of paranoid psychosis and anxiety disorder, as well as current treatment with a neuroleptic medication, were more common in patients with ictal fear. This study provides limited support for the thesis that ictal fear is associated with behavioral changes in epilepsy, particularly symptoms of anxiety, introversion, and paranoia

We correlated interictal (> 6 h after seizure) cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), neuropeptides, amino acids, and cortisol with self-report behavioral rating scales in 19 patients with medically intractable complex partial seizures. The Beck Depression Inventory, Spielberger Trait Anxiety Scale, and Personality Disorders Questionnaire-Revised [DSM-IIIR-based personality disorder (PD) rating scale] were used to assess behavior. There were no significant correlations between either HVA or 5-HIAA and behavioral scores. The strongest findings were the positive correlations between CSF levels of neuropeptide Y and depression and between CSF levels of cortisol and antisocial PD. Five other significant correlations were also found. There was no significant effect of the presence or levels of carbamazepine or phenytoin on those CSF neurochemicals that were associated with behavioral scores. This preliminary study suggests that certain behavioral features in epilepsy may have neurochemical markers

We administered a modified version of the Psychosensory-Psychomotor Phenomena Interview (PPPI) to 128 patients with complex partial seizures (CPS), 20 patients with generalized seizures, and 58 controls (30 normals, 28 back pain) to study the symptoms of partial seizures. The PPPI is a structured interview used by a physician to survey a spectrum of potential seizure symptoms. Use of the PPPI led to the following changes in diagnosis: 10 patients with generalized tonic-clonic seizures were found to have onset with simple partial seizures, 18 patients with complex partial seizures were found for the first time to have auras, and 4 patients with simple partial seizures were also found to have CPS. Overall, auras precede some CPS in 89% of patients. The PPPI led to recognition of more than twice the number of ictal symptoms than standard history and review of previous reports. Differences in symptom frequency (ictal and interictal) between the two seizure groups and between each seizure group and controls were studied. Although several significant associations were found, because of multiple statistical comparisons, results must be interpreted with caution. The PPPI is a valuable tool for examining paroxysmal symptoms in seizure patients, although time constraints limit its use in routine clinical practice