Claustrum hyperintensity: a rare radiological correlate in Niemann-Pick disease.

A 5-year-old male child of consanguineous parentage, without any adverse perinatal history, presented with progressive cognitive regression predominantly in the language and attention domains, for 2 years. He had simultaneous pyramidal and extrapyramidal involvement, frequent generalised tonic-clonic seizures and recurrent respiratory tract infections. Examination was significant for vertical supranuclear gaze palsy, coarse facial features and splenomegaly. Given the clinical features, in the background of consanguinity and mother's history of spontaneous pregnancy losses, inborn errors of metabolism were suspected. Following relevant investigations including tailored genetic study, Niemann-Pick disease type C (NPC) was diagnosed. Interestingly, MRI brain showed bilateral T2/fluid-attenuated inversion recovery claustrum hyperintensities, which are more commonly associated with autoimmune encephalitis and febrile infection-related epilepsy syndrome and not reported previously in NPC. Additionally, language regression as a presenting manifestation in NPC as opposed to classical dysarthria makes this case truly unique.

Dramatic Response to Pramipexole in Delayed-Onset Parkinsonism from Osmotic Demyelinating Syndrome.

Background: Delayed parkinsonism and dystonia are recognized phenomena in osmotic demyelinating syndrome (ODS). Dopamine receptor agonists and levodopa have been reported to benefit select patients. Case report: We report a patient with ODS with severe pseudobulbar deficits, parkinsonism and dystonia, poorly responsive to levodopa, who experienced a remarkable improvement with pramipexole. Discussion: A marked response to pramipexole with lack of response to levodopa suggests a pre-synaptic source for his deficits coupled with injuries to non-nigral compensatory structures. Highlights: This case highlights a dramatic response of osmotic demyelination-induced parkinsonism/dystonia to pramipexole. A lack of response to levodopa suggests deficits in the pre-synaptic nigral as well as non-nigral compensatory structures.

The psychopharmacology of pseudobulbar affect.

Pseudobulbar affect (PBA) is characterized by uncontrollable emotional episodes disconnected or disproportionate with mood, in association with an array of neurologic conditions. PBA is associated with disruption of descending control of brainstem motor circuitry and dysregulation of serotonergic and glutamatergic function. PBA has been historically under recognized, though advances resulting in more specific diagnostic criteria, validated rating scales, and an approved pharmacotherapy offer opportunities for improved treatment outcomes.

Safety, Tolerability, and Effectiveness of Dextromethorphan/Quinidine for Pseudobulbar Affect Among Study Participants With Traumatic Brain Injury: Results From the PRISM-II Open Label Study.

BACKGROUND: Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI). OBJECTIVE: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale. DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE). RESULTS: DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%). CONCLUSIONS: DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials. LEVEL OF EVIDENCE: II.

[Effects of GAO's neck acupuncture on swallowing function and quality of life in patients with post-stroke pseudobulbar palsy:a randomized controlled trial].

OBJECTIVE: To observe the effects of GAO's neck acupuncture combined with swallowing rehabilitation on swallowing function and quality of life in patients with post-stroke pseudobulbar palsy. METHODS: One hundred patients were randomly assigned in to an observation group and a control group, 50 cases in each one. The patients in the control group were treated with basic pharmaceutical treatment, including neurotrophy medication and free radical scavenging medication as well as swallowing rehabilitation; the patients in the observation group, on the basis of those in the control group, were treated with GAO's neck acupuncture at Fengchi (GB 20), Yiming (EX-HN 14), Gongxue (Extra), Lianquan (CV 23), Wai Jinjin Yuye (Extra), Tunyan (Extra), Zhiqiang (Extra), Fayin (Extra), once a day, five times a week for continuous eight weeks. The Repetitive saliva-swallowing test (RSST), standardized swallowing assessment (SSA) and swallow quality-of-life questionnaire (SWAL-QOL) before and after treatment in the two groups were observed; the relationship between disease location and frequency and efficacy of GAO's neck acupuncture was explored in the observation group. RESULTS: After treatment, the RSST, SSA and SWAL-QOL were superior to those before treatment (all P<0.01), with more significant results in the observation group (all P<0.01). The total effective rate was 91.7% (44/48) in the observation group, which was superior to 75.5% (37/49) in the control group (P<0.01). The frequency of disease onset was one in 11 patients and 2 and above in 37 patients in the observation group, and the efficacy of one onset of disease was 100.0% (11/11), which was superior to two and above of onset 89.2% (33/37, P<0.01). The number of patients with disease location at cortex and subcortex was 21, while that at capsula interna and basal ganglia was 27 in the observation group, the efficacy of two was similar (P>0.05). CONCLUSIONS: GAO's neck acupuncture combined with swallowing rehabilitation could effectively improve dysphagia and quality of life in patients with post-stroke pseudobulbar palsy. No correlation of lesion locations on acupuncture efficacy is observed, while onset frequency is inversely proportional to efficacy.

[TRANSIENT PSEUDOBULBAR SYNDROME IN UNILATERAL FRONTAL OPERCULAR INFARCTS]. / ÁTMENETI PSEUDOBULBARIS TÜNETCSOPORT EGYOLDALI FRONTÁLIS OPERCULARIS INFARKTUSOKNÁL.

The classic anterior (frontal) opercular syndrome (Foix-Chavany-Marie sy.) is a cortical pseudobulbar palsy mainly due to bilateral lesions of anterior brain operculum. In 2000 the authors had a 70-year old female patient with acute onset of swallowing and speaking difficulty. Neurological examination established a left facial central palsy, the palsy of the tongue and the soft palate, dysarthry, difficulty in chewing with left side hemiparesis. The CT scan showed a right side (one-sided) frontal opercular ischemic lesion. This event switched their attention especially to this group of cases and subsequently the authors collected 12 patients with these symptoms. Authors discuss the patomechanism of transient pseudobulbar palsy that occurs due to unilateral opercular lesion that the diaschisis effect might explain.

PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions.

BACKGROUND: Pseudobulbar affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA. METHODS: Participating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study-Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient's quality of life (QOL). Presence of PBA symptoms was defined as a CNS-LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded. RESULTS: PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs <13 (6.7 [2.5] vs. 4.7 [3.1], respectively; P<0.0001 two-sample t-test). A greater percentage of patients with CNS-LS ≥13 versus <13 were using antidepressant/antipsychotic medications (53.0% vs 35.4%, respectively; P<0.0001, chi-square test). CONCLUSIONS: Data from PRISM, the largest clinic-based study to assess PBA symptom prevalence, showed that PBA symptoms were common among patients with diverse neurological conditions. Higher CNS-LS scores were associated with impaired QOL and greater use of antipsychotic/antidepressant medications. These data underscore a need for greater awareness, recognition, and diagnosis of PBA.

Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments.

Pseudobulbar affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient's external circumstances and incongruent with the patient's internal emotional state. Recent data suggest disruption of cortico-pontine-cerebellar circuits, reducing the threshold for motor expression of emotion. Disruption of the microcircuitry of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression. Current evidence also suggests that serotonergic and glutamatergic neurotransmission play key roles. Although antidepressants have shown benefit, the supportive clinical data have often derived from small numbers of patients and unvalidated measures of PBA severity. Dextromethorphan/quinidine, the first FDA-approved PBA medication, is a novel therapy with antiglutamatergic actions. As life expectancy lengthens and the neurologic settings of PBA become more common, the need for treatment can be expected to increase.

[Regulating the governor Vessel and Conception Vessel for treatment of pseudobulbar palsy after stroke].

OBJECTIVE: To compare the therapeutic effect of method for regulating the Governor Vessel and Conception Vessel as well as routine needling method. METHODS: Sixty-four cases of pseudobulbar palsy after stroke were randomly divided into an observation group and a control group, 32 cases in each group. The observation group was treated with regulating the Governor Vessel and Conception Vessel, Tiantu (CV 22) through to Danzhong (CV 17), Shanglianquan (Extra), Baihui (GV 20) through to Naohu (GV 17), Fengfu (GV 16) were selected; the control group was treated with routine needling method with acupoints Yamen (GV 15), Lianquan (CV 23), Tongli (HT 5), Guanchong (TE 1). Scores of Watian drinking water test were observed before and after treatment, and therapeutic effects of two groups were compared. RESULTS: The effective rate of 87.5% (28/32) in the observation group was superior to that of 65.6% (21/32) in the control group (P < 0.05). Scores of Watian drinking water test in both groups were significantly decreased after treatment (both P < 0.01), and the degree of the decrease in the observation group was superior to that of control group (P < 0.01). CONCLUSION: Regulating the Governor Vessel and Conception Vessel has a significant therapeutic effect for treatment of pseudobulbar palsy after stroke, and superior to that of routine needling.

Herpes encephalitis presenting with an opercular syndrome and epilepsia partialis continua.

OBJECTIVES: The opercular syndrome is a rare form of pseudobulbar palsy that is characterized by automatic-voluntary dissociative weakness of the face in addition to weak masticatory and pharyngeal muscles. It is typically seen in the setting of an acute stroke or in association with various congenital malformations of the cortex. It has also been described rarely in association with herpes encephalitis but with an abnormal cerebrospinal fluid (CSF) cell count. METHODS: We report on a 65-year-old-man with an opercular syndrome associated with epilepsia partialis continua (EPC) secondary to acute herpes simplex virus encephalitis despite an initial near normal CSF analysis. RESULTS: Initial EEG was unremarkable while CSF analysis revealed changes suggestive of a traumatic tap. An opercular syndrome was diagnosed based on the classic presentation of dysarthria, facial diplegia, and hypersalivation, with corresponding MRI brain changes in the operculum. During admission, EPC developed, with continuous right facial twitching and an electroencephalographic correlate in the left centrotemporal region. The EPC initially responded to intravenous lorazepam. Phenytoin was then added for seizure prophylaxis. Herpes virus DNA was later on detected in the CSF. The patient improved with antiviral treatment except for very mild residual dysarthria. CONCLUSION: Neurologists should be aware of the possible predilection of the herpes simplex virus for the opercular area and the need to empirically treat for herpes encephalitis even in the setting of near normal initial CSF studies in patients with a suggestive clinical presentation.

[Amyotrophic lateral sclerosis: management of bulbar symptoms]. / Amyotrophe Lateralsklerose: Symptomatische Therapie bulbärer Symptome.

Symptomatic treatment of amyotrophic lateral sclerosis (ALS) is relevant in preventing complications and improving quality of life as long as curative therapies are still out of sight. About one third of ALS patients show disabling problems associated with dysarthria, dysphagia, sialorrhea, and a pseudobulbar affective disorder already in the early stages of ALS. A multidisciplinary approach is the cornerstone of symptomatic treatment of bulbar and pseudobulbar ALS features. Except for riluzole randomized controlled trials are lacking. Here, we review the current views with regard to epidemiology, pathophysiology, diagnosis, and practical aspects of treating bulbar and pseudobulbar symptoms.

Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect.

The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

Dextromethorphan/quinidine sulfate for pseudobulbar affect.

A new agent containing a combination of dextromethorphan (DM) and quinidine (Q) is currently under development for the treatment of pseudobulbar affect (PBA). PBA is a disorder of emotional regulation, characterized by uncontrollable outbursts of laughing and/or crying that are disproportionate to the emotions being experienced. The pathophysiology of PBA is currently unknown, although the disorder is thought to occur exclusively in the setting of neurological disease. The most influential theory on PBA posits that emotional outbursts are being generated autonomously in the brain stem due to loss of regulatory control by the frontal lobe. Although rarely life-threatening, PBA can have significant impact on patient quality of life, and thus merits treatment. There are currently no approved treatments for PBA. Several agents have been found to be effective in small placebo-controlled trials and case series, with the most commonly used agents being tricyclic antidepressants and selective serotonin reuptake inhibitors. Both these treatments are inexpensive and relatively low-risk, although the quality and quantity of data available on their efficacy are not optimal. DM has several pharmacological mechanisms of action relevant to the brain. It is an N-methyl-D-aspartate (NMDA) receptor antagonist, which prompted investigators to study its potential for slowing progression in amyotrophic lateral sclerosis (ALS), where glutamate toxicity is thought to be a factor. The combination agent DM/Q was developed to slow the metabolism of DM by P450 2D6 enzymes in the liver. DM/Q was not effective in slowing ALS progression, but patients noted that it helped to control their emotional outbursts, suggesting it might be useful as a treatment for PBA. DM is also a sigma-1 receptor agonist. These receptors are widely distributed in the brain, but probably most heavily in the limbic system, suggesting that DM may exert its emotion-controlling effects via these receptors. The endogenous ligands for sigma-1 receptors are not altogether known, although they appear to include gonadal steroids. DM/Q was recently shown to be effective in reducing the severity of PBA in two large studies of ALS and multiple sclerosis, which are probably the most common neurological settings. These are the largest treatment studies of PBA ever done. The agent was safe and relatively well tolerated. Further studies are being conducted to see if efficacy can be maintained with lower doses of quinidine. If DM/Q is approved by the U.S. Food and Drug Administration for treatment of PBA, it would be the first agent approved for this purpose. Currently, the antidepressants are probably the most attractive pharmacologic options for treatment of PBA. The choice of whether to use DM/Q in this setting will likely depend on individual patient factors as well as cost.

Familial and genetic associations in Worster-Drought syndrome and perisylvian disorders.

Worster-Drought syndrome (WDS) is a distinct clinical phenotype, comprising a congenital pseudobulbar palsy usually in association with a mild tetraplegia and often additional impairments. The phenotype is identical to that described in congenital bilateral perisylvian polymicrogyria syndrome (CBPS) and appears to have several different causes and a significant familial incidence. This study draws from a database of children with WDS phenotype or perisylvian polymicrogyria, held at a tertiary center. The findings suggest that genetic factors are important for a significant proportion of children and points to considerable genetic heterogeneity. There are grounds for considering WDS and perisylvian polymicrogyria as a spectrum of perisylvian malfunction.

Recognizing and treating common psychiatric disorders in multiple sclerosis.

BACKGROUND: The rate of depression and other psychiatric disorders is greater in multiple sclerosis (MS) than in other chronic conditions or neurologic diseases. This means that clinical neurologists seeing MS patients will frequently be engaged in the diagnosis and treatment of psychiatric distress. REVIEW SUMMARY: This review provides a summary of what is known about psychiatric dysfunction in MS. It offers information about the current views on the link between various psychiatric disorders and MS. More important, it offers suggestions on how the knowledge from existing research can be integrated into real-world practice. CONCLUSION: Clinicians need to understand the factors that influence the development of psychiatric disorders in MS, the relationship between disease-modifying therapies and psychiatric distress, and the issues surrounding the treatment of psychiatric conditions in MS. Thorough knowledge of psychiatric dysfunction and MS will allow the clinician to design an effective treatment regimen that helps patients cope with their disease.