Pathological laughter and crying: A case series and proposal for a new classification.

BACKGROUND: Disorders of laughter and crying (DLC) are seen in several neuropsychiatric conditions. Their nomenclature remains under debate. METHODS: We present the clinical and imaging findings of 17 patients with DLC and introduce a new classification based on phenomenology and pathogenesis. According to intensity and frequency of laughter and crying (observed behavioral output), patients were divided into hypoactive or hyperactive DLC and subdivided into 5 subtypes: sensory (positive and negative), motor (positive and negative), and mixed. The sensory subtype is represented by disorders of "feeling processing," whereas the motor subtype is represented by disorders of "emotion processing." "Positive" and "negative" describe elicitation by irritative vs destructive lesions, respectively. RESULTS: Among the patients studied, DLC resulted from ischemic stroke (n = 12), intracerebral hemorrhage (n = 2), gunshot wound (n = 1), amyotrophic lateral sclerosis (n = 1), or vestibular migraine (n = 1). Ten patients had lesions in the brainstem, 4 in the cerebral hemispheres, and 2 in sub-cortical-diencephalic structures. Six patients had negative motor DLC, 5 had positive sensory DLC, 4 had negative sensory DLC, and 2 had positive motor DLC. Phenomenology changed or progressed to mixed DLC in 7 patients. CONCLUSIONS: This novel phenomenological and pathomechanistic nomenclature explains all subtypes of DLC in neurologic, medical, and psychiatric conditions. Future studies are needed to validate it prospectively.

Neurologic presentations of fungal infections.

Fungal infections of the central nervous system (CNS) have a high rate of morbidity and mortality caused by several factors. Most importantly, the last three decades have witnessed a rising prevalence of susceptible hosts from the growing numbers of organ transplants, chemotherapy patients, and intensive care unit hospitalizations. Knowledge of CNS fungal infections including their symptoms and signs, required diagnostic studies, and treatment methods is imperative for all neurologists. This article provides an overview of the clinical features and laboratory findings of the major mycoses affecting the CNS and a focus on their neurologic presentations.

Ondansetron and seizures.

Experimental studies suggest that 5-hydroxytryptamine (5-HT) receptors play a role in epileptogenesis and seizure propagation. Ondansetron, a 5-HT(3) receptor antagonist, has been reported to have proconvulsant and anticonvulsant effects in animals. We describe three patients who developed seizures after receiving ondansetron. There were two females and one male. Ages ranged from 38-56 years. None had a previous or family history of seizures. Four milligrams (mg) of ondansetron was given intravenously for severe nausea and vomiting in association with migraine, gastritis, and diabetic ketoacidosis. A generalized tonic-clonic seizure occurred in each patient--12, 15, and 22 min after injection. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) were normal in all patients. Although no antiepileptic drugs were given, none had seizure recurrence subsequently. The temporal relationship between ondansetron administration and seizures, lack of EEG or MRI abnormalities, and absence of seizure recurrence suggest that the seizures were causally related to ondansetron in our patients.

The optic nerve.

The optic nerve is our most important cranial nerve. As it courses from the eyeball to the brain, it is divided into four segments: intraocular, intraorbital, intracanalicular, and intracranial. Four tests are primarily used to assess its functional integrity and detect optic nerve disorders. These tests are described along with key funduscopic findings. The clinical features of both common as well as notable disorders that occur along the four segments are presented. For example, papilledema and anterior ischemic optic neuropathy involve the intraocular segment, dysthyroid optic neuropathy or optic nerve sheath meningiomas affect the intraorbital segment, traumatic optic neuropathy is mainly within the intracanalicular segment, and pituitary tumors and suprasellar masses compromise the intracranial segment. Ancillary clinical symptoms and signs are highlighted that assist the neurologist in understanding and localizing each disorder along one of these segments. The chief means of confirming the diagnosis, often neuroimaging, are given, and common treatment modalities are provided.

IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event.

BACKGROUND: The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]). OBJECTIVE: To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years. METHODS: CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years. RESULTS: Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years. CONCLUSIONS: These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Subclavian artery dissection and triple infarction of the nervous system.

BACKGROUND: Subclavian artery dissection is a rare entity. It is usually associated with anomalous aortic vasculature. Only with trauma or catheterization procedures is subclavian artery dissection with normal aortic vasculature reported. PATIENT: We describe a patient with intrascapular pain, an occipital headache, and 3 distinct infarctions in the nervous system. He had spontaneous subclavian artery dissection with normal aortic vasculature. CONCLUSION: Subclavian artery dissections should be suspected in patients with intrascapular pain, occipital or cervical pain, and symptoms within the posterior circulation.

Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses.

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.