Benign nocturnal alternating hemiplegia of childhood: A new case with unusual findings

It has been described a neuro developmental disorder labelled “Benign nocturnal alternating hemiplegia of childhood” (BNAHC) characterized by recurrent attacks of nocturnal hemiplegia without progression to neurological or intellectual impairment. We report a female patient who at 11 months revealed a motionless left arm, unusual crying without impairment of consciousness and obvious precipitating factors. The attacks occur during sleep in the early morning with lack of ictal and interictal electroencephalographic abnormalities, progressive neurological deficit, and cognitive impairment. Unlike previous reports of BNAHC our patient come from a family with a history of both migraine, hemiplegic migraine, and sleep disorders. Our study remarks on the typical features described in previous studies and stresses the uncommon aspects that could help to identify the disorder which is likely to have been underestimated. Despite some clinical similarities between BNAHC and familiar hemiplegic migraine and alternating hemiplegia of childhood, the genetic analyses of our patient did not reveal genetic mutations found in both disorders.     

Benign nocturnal alternating hemiplegia of childhood: The first clinical report with paroxysmal events home‐video recordings

Benign familial nocturnal alternating hemiplegia of childhood (BNAHC) is a rare disorder characterized by recurrent attacks of hemiplegia, arising from sleep without progression to neurological or intellectual impairment. It is distinct from the malignant, relatively more common, alternating hemiplegia of childhood (AHC), complicated by developmental deterioration, cognitive impairment, and permanent neurological deficits such as choreoathetosis. The authors add a new case of BNAHC to the pertinent literature and report, for the first time, a video with the typical nocturnal hemiplegic attacks in order to improve knowledge about this disorder among child neurologists and pediatricians and increase the possibility of clarifying its pathogenesis and molecular basis. © 2008 Movement Disorder Society     

Benign nocturnal alternating hemiplegia of childhood: six patients and long-term follow-up.

Benign familial nocturnal alternating hemiplegia of childhood refers to recurrent attacks of hemiplegia arising from sleep, described in young children without neurologic or mental impairment. It is probably migraine related. The authors report two unrelated patients with nocturnal attacks starting at 22 and 31 months, followed by daytime episodes in one. The authors confirm the benign course of this disorder. It is distinct from the classic malignant form of alternating hemiplegia of childhood.     

Focal brain dysfunction in a 41-year old man with familial alternating hemiplegia

The acute pathophysiologic changes during hemiplegic spells and the long-term outcome of alternating hemiplegia remain obscure. In a 41-year-old male with familial alternating hemiplegia we found an increase in right frontal cerebral blood flow 3 h into a 5-h left hemiplegic episode. A repeat high-resolution brain SPECT study performed 26 h after the resolution of the left hemiplegia revealed normalization of the frontal blood flow accompanied by hyperperfusion in the right parietal lobe. An interictal SPECT scan several weeks later showed no asymmetries. Head CT and MRI scans were negative. Neuropsychologic assessment and neurologic examination revealed evidence of a diffuse disorder which predominantly involved the right hemisphere. To our knowledge, there are no previous correlative studies of serial highresolution brain SPECT with MRI, or of detailed neuropsychologic assessment, in adult patients with such an advanced course of alternating hemiplegia of childhood.     

Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3: a case report and pathophysiological considerations

We describe a case of a child suffering from alternating hemiplegia with a heterozygous p. E815K pathogenic variant of ATP1A3. The patient started to present abnormal eye movements in the first days of life, followed by the appearance at 2 months of dystonic episodes, and later on, by recurrent episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left‐sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms with familial hemiplegic migraine that may be associated with a pathogenic variant of ATP1A2.     

Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood

Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood. Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 7 6/12 years) using alpha[11C]methyl-L-tryptophan positron emission tomography (PET). The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient. The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 7 8/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 9 11/12 years). Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally. The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks. In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity. Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group. There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042). These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood. Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder.     

A population-based longitudinal study of risk factors for suicide attempts in major depressive disorder

No longitudinal study has examined risk factors for future suicide attempts in major depressive disorder in a nationally representative sample. The objective of this study was to investigate baseline sociodemographic characteristics, comorbid mental disorders, specific depressive symptoms, and previous suicidal behavior as potential risk factors for suicide attempts at 3 years follow-up. Data came from the national epidemiologic survey on alcohol and related conditions (NESARC), a large nationally representative longitudinal survey of mental illness in adults [Wave 1 (2001-2002); Wave 2 (2004-2005) n = 34,653]. Logistic regression examined associations between risk factors present at Wave 1 and suicide attempts at Wave 2 (n = 169) among individuals with major depressive disorder at baseline assessment (n = 6004). Risk factors for incident suicide attempts at Wave 2 (n = 63) were identified among those with major depressive disorder at Wave 1 and no lifetime history of suicide attempts (n = 5170). Results revealed specific comorbid anxiety, personality, and substance use disorders to be associated with incident suicide attempts at Wave 2. Comorbid borderline personality disorder was strongly associated with suicide attempts in all models. Several comorbid disorders were strongly associated with suicide attempts at Wave 2 even after adjusting for previous suicidal behavior, notably posttraumatic stress disorder (adjusted odds ratio (AOR) = 2.20; 95% confidence interval (95% CI) 1.27-3.83) and dependent personality disorder (AOR = 4.43; 95% CI 1.93-10.18). These findings suggest that mental illness comorbidity confers an increased risk of future suicide attempts in major depressive disorder that is not solely accounted for by past suicidal behavior.     

儿童交替性偏瘫一例

目的了解儿童交替性偏瘫(AHC)的诊断及治疗方法的合理选择。方法介绍我院收治的1例难治的儿童交替性偏瘫患儿的临床特点,检索国内外10年内的相关文献。结果本病的临床特点为反复发作性的偏瘫,睡眠后缓解,可有其他发作性症状,如发作性肌张力障碍、眼球运动异常和认知障碍等。氟桂利嗪是最常用的药物,托吡酯片、阿立哌唑也可用于治疗本病。结论本病是一种罕见的神经系统发作性疾病,临床表现多样,容易误诊,目前没有标准的治疗方法。     

Prevalence of body dysmorphic disorder in a German psychiatric inpatient sample

Body dysmorphic disorder (BDD) is a distressing or impairing preoccupation with an imagined or slight defect in appearance. Only a few studies have examined BDD prevalence in psychiatric settings. Prevalence rates vary widely and most studies have been conducted in outpatient samples. In the current study, we examined 155 adult psychiatric inpatients. Diagnostic criteria of BDD were assessed with the BDD module of the Structured Clinical Interview for DSM-IV. The prevalence of lifetime BDD was 2.6% (95% CI = 0.1-5.1%). Currently 1.9% of the patients suffered from BDD (95% CI = 0.0-4.0%). None of these patients were diagnosed with BDD on admission or during hospitalization. The BDD rates found in this study are considerably lower than lifetime and current prevalence rates reported by two other studies conducted in adult psychiatric inpatient settings ( [Grant et al., 2001] and [Conroy et al., 2008]). The differences may be explained by divergent sample compositions and variation in diagnostic measures. The findings of the current study underline the need for further studies examining BDD prevalence in psychiatric settings and suggest using a combination of screening questionnaire and follow-up interview to diagnose BDD.     

Altered DARPP-32 expression in the superior temporal gyrus in schizophrenia

Many neuroimaging studies have revealed structural abnormalities in the superior temporal gyrus (STG) in schizophrenia ( [Kasai et al., 2003b] and [Kasai et al., 2003a]; Sun et al., 2009). Neurophysiological studies of mismatch negativities (MMN) generated in the STG have suggested impaired function of N-methyl-d-aspartate (NMDA) receptors (Javitt et al., 1996). Although many postmortem studies have been conducted on the pathogenesis of schizophrenia, relatively few reports have studied molecular alterations in the STG ( [Bowden et al., 2008], [Deng and Huang, 2006], [Kang et al., 2009], [Katsel et al., 2005], [Le Corre et al., 2000], [Nudmamud and Reynolds, 2001] and [Sokolov et al., 2000]). The STG shows pronounced changes in gene expression when compared to other regions implicated in schizophrenia (Katsel et al., 2005). Dopamine and a cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) is thought to be closely associated with pathophysiological changes in the dopamine and glutamate systems in schizophrenia because, when activated by phosphorylation, DARPP-32 acts as a critical regulator of D1 dopamine receptor and NMDA receptor activity (Greengard et al., 1999). The molecular pathways involving DARPP-32 appear important in the pathogenesis of schizophrenia. Here, we show dramatic alterations in DARPP-32 expression in the STG of postmortem brains from patients with schizophrenia. To clarify the detailed histological and cellular expression of DARPP-32 in the STG in schizophrenia, we immunohistochemically examined postmortem brains by using specific antibodies. We compared the density of immunoreactive cells of the STG (BA22) from 11 schizophrenia patients with those from 11 age- and sex-matched controls, and found significantly lower densities of DARPP-32-immunoreactive (IR) cells and threonine (Thr) 34-phosphorylated DARPP-32-IR cells in the STG in the schizophrenia group. Thus, the DARPP-32-related pathogenesis in schizophrenia may be more severe in the STG than previously found in the prefrontal cortex.     

Alternating hemiplegia of childhood: New diagnostic options

A syndrome of alternating hemiplegia of childhood (AHC) is a rare disorder first presented in 1971. AHC is characterized by transient episodes of hemiplegia affecting either one or both sides of the body. Age of onset is before 18 months and the common earliest manifestations are dystonic or tonic attacks and nystagmus. Hemiplegic episodes last minutes to days and the frequency and duration tend to decrease with time. Motor and intellectual development is affected, deficits may also develop later. Epileptic seizures occur in some patients. Neuroimaging of the brain usually reveals no abnormalities. The variability of individual clinical presentations and evolution of symptoms have made diagnosis difficult. Therefore the problems of misdiagnosis could account for the low prevalence of this syndrome. This paper hopes to present actual data on AHC, especially of the results of genetic research and new diagnostic tools.     

There is more than the amygdala: potential threat assessment in the cingulate cortex

Fear conditioning with its neurological basis in the amygdala and associated structures provides an important model of anxiety disorders. However, this review will argue for a distinction between fear-provoking immediate and anxiety-provoking potential threats, with the amygdala processing immediate threats and the cingulate cortex (and insular) processing potential threats. Four independent but related literatures are reviewed to bolster this argument: (1) rodent remote contextual fear conditioning, (2) symptom provocation in obsessive compulsive disorder (OCD), (3) fMRI investigations of risk assessment, and (4) behavioural and neurological studies of precautionary reasoning. These four literatures converge in suggesting that the cingulate cortex (and in more specific instances the insula) underlie potential threat assessment, providing support for a number of recent models posting the existence of a separate potential threat system that is dysfunctional in obsessive compulsive disorder (e.g., [Szechtman and Woody, 2004] and [Woody and Szechtman, 2011]).     

Emerging adulthood in developmental co-ordination disorder: parent and young adult perspectives

Recent research widely acknowledges that developmental co-ordination disorder (DCD) is a pervasive and enduring disorder, which persists into adolescence and adulthood ( [Cousins and Smyth, 2003] and [Kirby et al., 2008]). However, few studies have given detailed consideration to the range and level of functioning difficulties in emerging adults with DCD, and no studies to date have gained a parental perspective.Current functioning of 19 young adults with DCD was examined using the Adult Dyspraxia/DCD Checklist (ADC, Kirby, Edwards, Sugden, & Rosenblum, 2010) and parents’ views of their child's current functioning was also obtained. Results suggest that whilst some motor skills such as handwriting continue to impact in emerging adulthood, not all skills are as problematic, such as self-care skills. Additionally, executive functioning, and social skills seem to be a key areas of concern for both young adults and their parents. Results provide guidance for areas of intervention that need to be considered, especially focusing on executive functioning skills. Also they highlight the need for gathering information from more than one source to gain a complete picture of functioning.     

三例儿童交替性偏瘫的回顾性分析

目的探讨儿童交替性偏瘫病因、临床特点、治疗效果。方法回顾性分析3例儿童交替性偏瘫患者的病因、临床表现及疗效。结果本组3例患者起病年龄均小于18个月,反复发作的交替性偏瘫；进行性的智能障碍,其中1例伴有短暂眼球震颤及眼球活动障碍,1例伴有张力障碍性姿势异常；睡眠可缓解无力及锥体外系症状,应用氟桂嗪治疗后,2例患者发作频率及持续时间降低,1例无效。结论本病病因不明,多为散发,临床表现为18月内起病的发作性交替性偏瘫,辅助检查无特征性改变,氟桂利嗪治疗部分有效。     

Face and object imagery in congenital prosopagnosia: A case series

It has been reported that congenital prosopagnosics may have a general imagery deficit or an imagery deficit specific to faces. However, much of this evidence is based on self-report questionnaires, rather than experimentally based testing ( [Grüter et?al., 2007] and [Grüter et?al., 2009]). This study tested face and non-face based imagery in a case series of congenital prosopagnosics, utilising both questionnaire based and forced choice accuracy measures. Our findings indicate that all the prosopagnosics showed impaired face based imagery, which contrasted with normal performance on imagery of objects and colours - a pattern that is consistent with reports of acquired prosopagnosia ( [Barton, 2008] and [Michelon and Biederman, 2003]). Given all our experimentally based testing indicated face imagery impairments, despite no such problems being seen on self-report questionnaires, we would argue that testing based only on the latter must be interpreted with some caution. Overall, we would advocate that our findings demonstrate a category specific visual imagery impairment in congenital prosopagnosia, such that general imagery skill can be intact in such cases.     

Regional differences and secular trends in the incidence of epilepsy in Finland: a nationwide 23-year registry study

Purpose: Regional variations and temporal trends in the incidence of new‐onset epilepsy are clinically important and may offer clues on how to prevent epilepsy. Methods: We examined regional differences and secular trends in the incidence of new‐onset epilepsy in the Finnish population based on the nationwide full‐refundable antiepileptic drug registry and the population registry in the years 1986–2008. Key Findings: The overall incidence of epilepsy was significantly higher in eastern Finland than in middle [risk ratio (RR) 1.08 (95% confidence interval, CI 1.05–1.12)), p < 0.0001] and western Finland [RR 1.32 (1.30–1.35), p < 0.0001] but it was declining from 1986 to 2008 in all regions [RR 0.83 (0.81–0.84), p < 0.0001]. The mean annual decline was 0.6%. Although the incidence of epilepsy was falling from 1986 to 2008 in childhood [annual decline 1.9%, RR 0.80 (0.75–0.86), p < 0.0001] and in middle age [annual decline 0.8%, RR 0.88 (0.84–0.93), p < 0.0001], it increased significantly in the elderly (age 65 years or older) in all of Finland [annual increase 3.5%, RR 1.25 (1.18–1.33), p < 0.0001], and particularly in east versus west Finland [RR 1.48 (1.42–1.55), p < 0.0001]. As a result, starting with the year 2000, the incidence rate of epilepsy was higher in the elderly than in children for all of Finland. Significance: In view of the falling incidence of epilepsy in childhood and middle‐age in all of Finland from 1986 to 2008, the significant increase in the incidence of epilepsy in the elderly is of concern. The regional increase of epilepsy may offer clues for allocating resources and, possibly, population epileptogenesis between west and east Finland and for strategies to prevent epilepsy in the elderly.     

儿童交替性偏瘫六例分析

目的探讨儿童交替性偏瘫（ＡＨＣ）的临床特点及治疗方法。方法对６例ＡＨＣ患儿的临床资料进行分析。结果６例患儿的临床特征为出生后１８个月起内病，频繁发作，持续数分钟至数小时；短暂的眼球震颤，肌张力异常，舞蹈徐动样动作，植物神经机能紊乱和认知机能减退；睡眠可缓解无力及锥体外系症状。应用氟桂嗪治疗后，１例患儿发作完全停止，其余５例患儿均显示发作频率和持续时间降低。结论本病的主要特征为１８个月内起病的发作性交替性偏瘫，伴锥体外系症状及智力障碍，氟桂嗪治疗本病有效     

Ocular motor features of alternating hemiplegia of childhood.

A 14-month-old boy with alternating hemiplegia of childhood, an idiopathic disorder of early childhood causing episodic hemibody tonic spasms and hemiplegia, showed repetitive jerks of abduction of the ipsilateral eye during the spells. The mechanism of this ocular motor abnormality is unknown but may be unique to this disorder.     

The clinical spectrum associated with ATP1A2 variants in Chinese pediatric patients

PurposeTo evaluate the clinical spectrum associated with ATP1A2 variants in Chinese children with hemiplegia, migraines, encephalopathy or seizures.MethodsSixteen children (12 males and 4 females), including ten patients with ATP1A2 variants whose cases had been published previously, were identified using next-generation sequencing.ResultsFifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant focal epilepsy. Thirteen patients had DD (developmental delay). The onset of febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant ATP1A2 variant, p.G855E.ConclusionsThe known genotypic and phenotypic spectra of Chinese patients with ATP1A2-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2.