Faculty Bibliography

BACKGROUND: The two-thirds of patients with epilepsy who become seizure-free have a quality of life (QOL) similar to the general population. The major treatment challenge is patients with refractory epilepsy. Whereas neurologists typically focus on seizure reduction in the treatment of these patients, results of studies relating seizure frequency to QOL are conflicting. As depression is associated with reduced QOL in epilepsy and antiepileptic medications (AEDs) can cause depression, it is important to determine the relative roles of depression and seizure frequency in QOL in refractory epilepsy. METHODS: Prospective evaluation was conducted of patients with refractory epilepsy being admitted to an inpatient video-EEG monitoring unit. The impact of clinical variables (age, sex, marital status, seizure frequency, duration and type of seizure disorder, seizure localization, number of AEDs, depression) on QOL was analyzed. RESULTS: Depression was a powerful predictor of QOL (n = 122, beta = -35.8, p < 0.0001). No other variable predicted QOL. Depression was common (54%), severe (19% with suicidal thoughts), underdiagnosed (37%), and largely untreated (17% on antidepressants). CONCLUSIONS: Treatment of depression may be inadequately prioritized in the management of intractable epilepsy

Acute pathologic neurologic laughter has been described as an ictal phenomenon in epilepsy, as a result of electrical brain stimulation to the cortex and to deep brain structures, in brain tumors, and in stroke. We report what is, to our knowledge, the first report of a case of postictal pathologic laughter. Previously diagnosed with medically refractory complex partial seizures, our patient was admitted to the hospital with phenytoin toxicity. During video-EEG monitoring she experienced multiple brief absence seizures as well as a prolonged episode of absence status epilepticus. Immediately following cessation of the seizure she began to laugh. Her laughter was mirthful and infectious. This lasted several minutes and was followed immediately by several minutes of crying and then a return to normal. We propose that diffuse cortical inhibition led to release of subcortical structures involved in emotional expression. Possible neural substrates of laughter are discussed

Peri-ictal behavioral and cognitive changes contribute substantially to disability and distress among people with epilepsy. Psychosis, depression, and suicide may all occur as complications of seizures. Greater appreciation and understanding of the peri-ictal period is clinically important and might open novel therapeutic windows. At the same time this period provides a model for understanding basic mechanisms underlying mood and thought disorders and the substrates of cognition, volition, emotion, and consciousness. This review will discuss behavioral and cognitive antecedents of seizures, including the preictal milieu, reflex seizures, and self-induced seizures. Behavioral and cognitive treatment approaches that have been undertaken are reviewed. Both acute and delayed postictal emotional, behavioral, and cognitive changes will be discussed. Finally, possible mechanisms by which epileptic brain activity and behavior may modify each other are considered

OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed

OBJECTIVE: To review findings from transcranial magnetic stimulation (TMS)-induced motor evoked potentials in normal subjects, in various neurological diseases and with pharmacologic manipulation. METHODS: MEDLINE was searched to identify pertinent articles and articles referenced therein were also reviewed. RESULTS: TMS is a safe and non-invasive technique which has been used widely in the study of corticospinal and corticocortical connectivity as well as in the assessment of basal ganglia disorders, diffuse diseases, and neuropharmacology. CONCLUSIONS: TMS motor measures have utility in examination of brain structure and function within and beyond the corticospinal tract. These measures have both research and clinical applications

BACKGROUND:Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). OBJECTIVE:The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. METHODS:Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. RESULTS:Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. CONCLUSIONS:BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 International Parkinson and Movement Disorder Society.