Limb-specific thalamocortical tracts are impaired differently in hemiplegic and diplegic subtypes of cerebral palsy.

Thalamocortical pathways are considered crucial in the sensorimotor functioning of children with cerebral palsy (CP). However, previous research has been limited by non-specific tractography seeding and the lack of comparison between different CP subtypes. We compared limb-specific thalamocortical tracts between children with hemiplegic (HP, N = 15) or diplegic (DP, N = 10) CP and typically developed peers (N = 19). The cortical seed-points for the upper and lower extremities were selected (i) manually based on anatomical landmarks or (ii) using functional magnetic resonance imaging (fMRI) activations following proprioceptive-limb stimulation. Correlations were investigated between tract structure (mean diffusivity, MD; fractional anisotropy, FA; apparent fiber density, AFD) and sensorimotor performance (hand skill and postural stability). Compared to controls, our results revealed increased MD in both upper and lower limb thalamocortical tracts in the non-dominant hemisphere in HP and bilaterally in DP subgroup. MD was strongly lateralized in participants with hemiplegia, while AFD seemed lateralized only in controls. fMRI-based tractography results were comparable. The correlation analysis indicated an association between the white matter structure and sensorimotor performance. These findings suggest distinct impairment of functionally relevant thalamocortical pathways in HP and DP subtypes. Thus, the organization of thalamocortical white matter tracts may offer valuable guidance for targeted, life-long rehabilitation in children with CP.

Adult hemiconvulsive hemiatrophy syndrome: a novel clinicoradiologic disorder in adults.

The association of focal motor seizures with cerebral hemiatrophy is a recognised rare paediatric syndrome known as 'hemiconvulsion, hemiatrophy and epilepsy' (HHE). To date, HHE has not been reported in adults. We present four adult patients with striking similarities to HHE, following alcohol withdrawal in chronic alcoholics. We document the imaging findings in the acute and subacute phases, discuss the underlying mechanisms and present a hypothesis regarding the pathophysiology.

Screening and validation of the iris manifestation among patients with hemiplegia - an observational study.

OBJECTIVES: Understanding and validating the science behind traditional diagnostic methods is a niche area to be explored. Iris diagnosis is one such valuable diagnostic tool used in Naturopathy. In the current study, we have assessed and documented the iris changes observed among patients with hemiplegia with respect to the iridology chart. METHODS: We recruited 35 patients with hemiplegia which includes both genders. Iris image was captured by Angel Kiss New 5.0MP Iridology Camera with Pro Iris Analysis Software. Lesion characters, such as open lesion, closed lesion, spot, furrow, radii solaris, intestinal crypts etc., in the iris were noted along with its various characteristics in an excel sheet in numerical order for analysis. RESULTS: Majority of the included patients were male (n=30) and the mean age of the patients was 46 years. The most common iris lesions noted were radii solaris and intestinal crypt in the cerebrum and cerebellum regions. Other notable lesions include open lesion, closed lesion, brown spot, hole and nerve ring. ROC analysis for selected iris lesions showed that intestinal crypt (AUC=0.82, p=0.01) and radii solaris (AUC=0.62, p=0.04) to be potential markers for hemiplegia. CONCLUSIONS: Two common lesions observed in patients with hemiplegia are radii solaris and intestinal crypt, corresponding to the cerebrum and cerebellum regions of the iris. Future studies with larger sample size would help warrant our current findings, and also the possible application of iris diagnosis as an early diagnostic marker for hemiplegia.

Different temporal weight-bearing tendencies of persons with right and left hemiplegia while sitting in a wheelchair.

The tendency of persons with hemiplegia to sit for prolonged periods can cause excessive interface pressure (IP) on their buttocks. Due to the different neuromusculoskeletal conditions, different buttock IP relief methods are required for persons with left hemiplegia (LH) and right hemiplegia (RH). Therefore, this study investigates temporal characteristics of IP on the right and left buttocks for RH, LH, and able-bodied individuals (AB) sitting in a wheelchair for 30 min. Thirty-five males participated in the study: 13 LH, 12 RH, and 10 AB. In the initial adjustment phase, the participants maintained an erect sitting posture for 7 min (2 min for posture and 5 min for creep adjustments). After the adjustments, experiments were conducted for 30 min to measure the IP. In the experiments, significant right-sided asymmetries of the mean IP were found for each group (P < 0.05). The right buttocks of LH exhibited significantly more right-sided asymmetry of the mean IP than that of AB (p < 0.01). Moreover, the right buttocks of RH exhibited insignificant asymmetry of the mean IP compared to that of AB (p >0.21). The peak IPs of RH and LH were significantly higher than those of AB (p <0.05), and temporal changes of the mean and peak IP of hemiplegia were significant (p <0.05) and not significant (p >0.05), respectively. The RH exhibited affected-side weight-bearing based on the mean IP. In contrast, the LH relieved the mean IP on the affected-side buttock. Due to the right-sided asymmetric mean and high peak IP, hemiplegia in acute and recovery stages using wheelchairs can cause ulceration. Therefore, different rehabilitation approaches are required for the RH and LH to reduce the peak IP and avoid an uneven distribution of the mean IP.

Turning duration and steps predict future falls in poststroke hemiplegic individuals: A preliminary cohort study.

Introduction: Turning was reported as one of the activities that most frequently leads to falling among stroke patients. This study investigated whether the duration and steps of a 180° turn while walking can distinguish retrospective fallers from non-fallers and predict future falls in a 1-year period in patients with poststroke hemiplegia. Methods: Thirty stroke patients were recruited. They were instructed to get up from a chair, walk straight 3 m, turn around, and return to seated position to assess the 180° walking-turn task. Turning performance was measured by two inertial sensor units of Physilog. Turn duration and steps were recorded for analysis. The numbers of retrospective and prospective falls were also obtained. Results: No significant difference was observed between retrospective stroke fallers and non-fallers in turn duration and steps. Turn duration and steps were significantly greater in prospective stroke fallers than in non-fallers. The cutoff turn duration of 4 s (area under the curve 0.75, 95% CI: 0.56-0.93, sensitivity 67%, specificity 80%, p =.04) and turn step of 7 steps (area under the curve 0.73, 95% CI: 0.51-0.94, sensitivity 56%, specificity 85%, p =.05) were found to most accurately predict prospective stroke fallers from non-fallers. Conclusions: Turn duration and steps were unable to discriminate between retrospective fallers and non-fallers but could predict prospective falls in patients with stroke. More than 4 s or 7 steps to complete a 180° turn while walking can be a predictor for patients with stroke at an increased risk of falling.

Long-term follow-up and novel genotype-phenotype analysis of monozygotic twins with ATP1A3 mutation in Alternating Hemiplegia of Childhood-2.

Alternating Hemiplegia of Childhood (AHC) is a rare disorder characterized by frequent, transient attacks of hemiplegia involving either side of the body or both in association to several other disturbances including dystonic spells, abnormal ocular movements, autonomic manifestations, epileptic seizures and cognitive impairment. The clinical manifestations usually start before the age of 18 months. Two forms of the disorder known as AHC-1 (MIM#104290) and AHC-2 (MIM#614820) depends on mutations in ATP1A2 and ATP1A3 genes respectively, with over 75% of AHC caused by a mutation in the ATP1A3 gene. Herewith, we report serial clinical follow-up data of monozygotic (MZ) twin sisters, who presented in early life bath-induced dystonia, signs of acute encephalopathy at the age of 2 years, hemiplegic spells, and motor dysfunction after the age of 3 years, and in young/adult frequent episodes of headache with drastic reduction of paroxysmal motor attacks. The molecular analysis revealed a known pathogenic variant p.Asn773Ser (rs606231437) in ATP1A3 gene associated with an unusual and moderate AHC-2 phenotype, with mild cognitive impairment and lack of epilepsy. The aim of this study is to analyze the clinical phases of the MZ twins, and to investigate the novel genotype-phenotype correlation.

Influence of back support shape in wheelchairs offering pelvic support on asymmetrical sitting posture and pressure points during reaching tasks in stroke patients.

Many poststroke hemiplegic patients have an asymmetrical wheelchair-sitting posture. This study aimed to investigate the impact of different back support shapes on asymmetrical sitting posture and pressure points among poststroke hemiplegic patients during an activities of daily living-related reaching task. This study included 23 poststroke hemiplegic patients who performed tasks that involved the movement of objects using the unaffected upper limb to the affected side while sitting in a conventional wheelchair (C-WC) with a flat back support or a wheelchair providing pelvic and thoracic support (P-WC). Body alignment angles from video images and pressure distribution on supporting surfaces were measured using a two-dimensional motion analysis software (Dartfish) and a pressure mapping system (FSA). Regarding movement performance, although postural asymmetry increased in both wheelchair types, the degree of postural variation was smaller with P-WC use than C-WC use (p < 0.05), with partly reduced postural asymmetry. With P-WC, one-sided ischial asymmetrical pressure was significantly less after the movement (p < 0.05). In conclusion, P-WC's back support shape contributed to a decrease in postural asymmetry for pelvic girdle support both at rest and during movement. This highlights the importance of a wheelchair back support shape and may help to increase the quality of activities of daily living movement in poststroke hemiplegic patients in wheelchairs.

Magnetic resonance imaging volumetric analysis in patients with Alternating hemiplegia of childhood: A pilot study.

Quantitative MRI is increasingly being used as a biomarker in neurological disorders. Cerebellar atrophy occurs in some Alternating Hemiplegia of Childhood (AHC) patients. However, it is not known if cerebellar atrophy can be a potential biomarker in AHC or if quantitative MRI is a reliable method to address this question. Here we determine the reproducibility of an MRI-volumetrics method to investigate brain volumes in AHC and apply it to a population of 14 consecutive AHC patients (ages 4-11 years). We studied method reproducibility in the first 11 patients and then performed correlation of cerebellar volumes, relative to published normal population means, with age in all 14. We used FreeSurfer 6.0.0 to automatically segment MRI images, then performed manual resegmentation correction by two different observers. No significant differences were observed in any of ten brain regions between the two reviewers: p > .591 and interclass Correlation Coefficient (ICC) ≥0.975 in all comparisons. Additionally, there were no significant differences between the means of the two reviewers and the automatic segmentation values: p ≥ .106 and ICC ≥0.994 in all comparisons. We found a negative correlation between cerebellar volume and age (R = -0.631, p = .037), even though only one patient showed any cerebellar atrophy upon formal readings of the MRIs by neuroradiology. Sample size did not allow us to rule out potential confounding variables. Thus, findings from this cross-sectional study should be considered as exploratory. Our study supports the prospective investigation of quantitative MRI-volumetrics of the cerebellum as a potential biomarker in AHC.

White matter and cerebellar involvement in alternating hemiplegia of childhood.

OBJECTIVE: To determine whether brain volumetric and white matter microstructural changes are present and correlate with neurological impairment in subjects with alternating hemiplegia of childhood (AHC). METHODS: In this prospective single-center study, 12 AHC subjects (mean age 22.9 years) and 24 controls were studied with 3DT1-weighted MR imaging and high angular resolution diffusion imaging at 3T. Data obtained with voxel-based morphometry and tract-based spatial statistics were correlated with motor impairment using the International Cooperative Ataxia Rating Scale (ICARS) and Movement and Disability sub-scales of Burke-Fahn-Marsden Dystonia Rating Scale (BFMMS and BFMDS). RESULTS: Compared to healthy controls, AHC subjects showed lower total brain volume (P < 0.001) and white matter volume (P = 0.002), with reduced clusters of white matter in frontal and parietal regions (P < 0.001). No significant regional differences were found in cortical or subcortical grey matter volumes. Lower cerebellar subvolumes correlated with worse ataxic symptoms and global motor impairment in AHC group (P < 0.001). Increased mean and radial diffusivity values were found in the corpus callosum, corticospinal tracts, superior and inferior longitudinal fasciculi, subcortical frontotemporal white matter, internal and external capsules, and optic radiations (P < 0.001). These diffusion scalar changes correlated with higher ICARS and BFMDS scores (P < 0.001). INTERPRETATION: AHC subjects showed prevalent white matter involvement, with reduced volume in several cerebral and cerebellar regions associated with widespread microstructural changes reflecting secondary myelin injury rather than axonal loss. Conversely, no specific pattern of grey matter atrophy emerged. Lower cerebellar volumes, correlating with severity of neurological manifestations, seems related to disrupted developmental rather than neurodegenerative processes.

Hippocampal diaschisis contributes to anosognosia for hemiplegia: Evidence from lesion network-symptom-mapping.

Anosognosia for hemiplegia (AHP) is known to be associated with lesions to the motor system combined with varying lesions to the right insula, premotor cortex, parietal lobe or hippocampus. Due to this widespread cortical lesion distribution, AHP can be understood best as a network disorder. We used lesion maps and behavioral data (n â€‹= â€‹49) from two previous studies on AHP and performed a lesion network-symptom-mapping (LNSM) analysis. This new approach permits the identification of relationships between behavior and regions connected to the lesion site based on normative functional connectome data. In a first step, using ordinary voxel-based lesion-symptom mapping, we found an association of AHP with lesions in the right posterior insula. This is in accordance with previous studies. Applying LNSM, we were able to additionally identify a region in the right posterior hippocampus where AHP was associated with significantly higher normative lesion connectivity. Notably, this region was spared by infarction in all patients. We therefore argue that remote neuronal dysfunction caused by disrupted functional connections between the lesion site and the hippocampus (i.e. diaschisis) contributed to the phenotype of AHP. An indirect affection of the hippocampus may lead to memory deficits which, in turn, impair the stable encoding of updated beliefs on the bodily state thus contributing to the multifactorial phenomenon of AHP.

Propranolol Treatment for Infantile Hemangiomas: Short-Term Adverse Effects and Follow-Up to Age Two.

OBJECTIVE: To analyse the short-term adverse effects (AEs) of propranolol in the treatment of infantile hemangiomas (IHs) and their relevant factors, as well as the relationship between child growth and propranolol. METHODS: A total of 506 patients with confirmed or suspected IHs were enrolled, and a total of 439 cases were included in the study. Short-term AEs were analysed using single-factor analysis and binary logistic regression. Out of 439 patients, 292 were enrolled to examine the effect of propranolol on 2-year-olds' height and body weight (BW), by comparison with reference range and among groups. Spearman rank correlation analysis was used to determine the relationship between BW, height, and duration of propranolol treatment. RESULTS: Among 439 patients, 70 (16.0%) experienced AEs. Among them, 48 had gastrointestinal (GI) symptoms, 23 had central nervous system (CNS) symptoms, 8 had both symptoms above, and 7 had other symptoms. Most of the AEs occurred on the starting day (day 0), and 6 children's AEs were transient. Starting age of no older than 3 months led to more CNS symptoms, and starting age of older than 3 months was a protective factor against CNS symptoms, with an OR value of 0.303 (0.117-0.783). Height and BW of 292 two-year-old children were no less than the reference levels, although those of 3 females and 1 male were less than the average -2 standard deviation (-2SD). The height and BW of the children at the age of two was not related to the length of time of propranolol treatment. CONCLUSION: Oral propranolol has a good tolerance in the treatment of IHs. Oral propranolol exerts more adverse effects on the CNS of lower age children, and it has exhibited no effect on the growth of two-year-old children.

Botulinum Toxin Injection in Children with Hemiplegic Cerebral Palsy: Correction of Growth through Comparison of Treated and Unaffected Limbs.

Botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP) may negatively affect muscle growth and strength. We injected BoNT-A into the affected limbs of 14 children (4.57 ± 2.28 years) with hemiplegic CP and exhibiting tip-toeing gait on the affected side and investigated the morphological alterations in the medial head of the gastrocnemius muscle (GCM). We assessed thickness of the GCM, fascicle length, and fascicle angle on the affected and unaffected sides at baseline at 4 and 12 weeks after BoNT-A injections. The primary outcome measure was the change (percentage) in GCM thickness in the affected side treated with BoNT-A in comparison with the unaffected side. The percentage of treated GCM thickness became significantly thinner at 4 and 12 weeks after BoNT-A injection than baseline. However, the percentage of fascicle length and angle in treated limbs showed no significant change from baseline 4 and 12 weeks after the injection. BoNT-A injections might reduce muscle thickness in children with spastic hemiplegic CP. Fascicle length and angle might not be affected by BoNT-A injections after correction of normal growth of the children.

A novel lethal recognizable polymicrogyric syndrome caused by ATP1A2 homozygous truncating variants.

Polymicrogyria is a heterogeneous malformation of cortical development microscopically defined by an excessive folding of the cortical mantle resulting in small gyri with a fused surface. Polymicrogyria is responsible for a wide range of neurological symptoms (e.g. epilepsy, intellectual disability, motor dysfunction). Most cases have a supposed environmental clastic vascular or infectious origin but progress in genomics has revealed new monogenic entities. We report four cases from two independent families sharing a common recognizable lethal syndromic polymicrogyria of autosomal recessive inheritance. Beyond diffuse polymicrogyria detected prenatally, pathological examination revealed a common pattern associating meningeal arterial calcifications, necrotic and calcified areas in basal ganglia, dentato-olivary dysplasia and severe hypoplasia/agenesis of the pyramidal tracts. In all affected cases, exome sequencing showed a pathogenic homozygous nonsense ATP1A2 variant. This resulted in absence of immunodetectable ATP1A2 protein in two brains analysed. ATP1A2 encodes the alpha-2 isoform of the Na+/K+-ATPase, which is highly expressed in brain tissues and has previously been related to familial hemiplegic migraine (MIM#602481) and alternating hemiplegia of childhood (MIM#104290). Through the description of this genetic entity, we emphasize the possibility of dual mode of transmission for disease-causing genes and provide the key neuropathological features that should prompt geneticists to test for mutations in the ATP1A2 gene.

Focal Status Epilepticus-Related Unilateral Brain Edema: Magnetic Resonance Imaging Study of Children in Southwest China.

BACKGROUND: Unilateral brain edema is a rare peri-ictal imaging abnormality related to focal status epilepticus. We present the largest series of these patients, describe their clinical features and magnetic resonance imaging (MRI) findings, and analyze the possible underlying pathophysiology. METHODS: We reviewed the medical records in Southwest China's largest tertiary's children's medical center from 2011 to 2017. Patients with focal status epilepticus were included if acute-phase cerebral MRI showed unilateral edematous swelling of the epileptic hemisphere. RESULTS: Eleven children were included. The age at which the patients presented with status epilepticus ranged from seven months to 10.8 years. All patients showed prolonged clonic seizures with marked unilateral predominance followed by hemiplegia of the ipsilateral limbs. The seizure duration ranged from one to 72 hours. All patients showed hyperintensities on T2-weighted images and diffusion-weighted images involving the whole pathologic hemisphere. Three patients showed involvement of the contralateral cerebellar hemisphere and one showed hippocampal herniation. Magnetic resonance angiography of the brain was performed in seven patients, among which three showed dilation of the affected hemispheric arteries. Three patients underwent follow-up MRI, and all the examinations revealed ipsilateral cerebral hemisphere atrophy. CONCLUSIONS: Focal status epilepticus may cause unilateral brain edema, and cytotoxic edema probably plays an important role in the pathophysiology of brain injury.

Mills' syndrome revisited.

Mills' syndrome is an idiopathic, slowly progressive, spastic hemiparesis. We describe three cases that have been under review for a minimum of 11 years (range 11-19). In all patients, symptoms started in a leg, with a mean age of onset of 59 years (range 53-63). The only abnormality on laboratory investigations was a mildly elevated CSF protein in one case. MRI demonstrated focal T2 hyper-intensity located eccentrically in the cervical cord ipsilateral to the symptomatic side. No cerebral abnormality was demonstrated. Whilst visual and somatosensory evoked potentials were unremarkable, motor evoked potentials were abnormal in all patients: central motor conduction times were significantly prolonged unilaterally in two patients and bilaterally but asymmetrically in the third. Beta-band (15-30 Hz) intermuscular coherence, a potentially more sensitive method of assessing upper motor neuron integrity, was absent unilaterally in one patient and bilaterally in the other two. One patient developed amyotrophy and thus a picture of amyotrophic lateral sclerosis after 16 years, suggesting that Mills' syndrome is part of the motor neuron disease spectrum. Both amyotrophy and subclinical contralateral upper motor neuron disease can therefore be features of Mills' syndrome. However, even with the most sensitive electrodiagnostic techniques, unilateral upper motor neuron disease can remain the only abnormality for as long as 10 years. We conclude that whilst Mills' syndrome should be classified as a motor neuron disorder, it is a distinct nosological entity which can be distinguished from amyotrophic lateral sclerosis, upper motor neuron-dominant amyotrophic lateral sclerosis and primary lateral sclerosis. We propose diagnostic criteria for Mills' syndrome, and estimate a point prevalence of at least 1.2:1,000,000 based on our well-defined referral population in the North of England.

Alternating Hemiplegia of Childhood in Two Adult Patients with a Mild Syndrome.

We describe the cognitive-behavioral functioning of two adult patients with a mild form of alternating hemiplegia of childhood (AHC). AHC is a rare, chronic neurodevelopmental syndrome manifesting in infancy or early childhood, with recurrent hemiplegic or hemidystonic attacks, various nonepileptic paroxysmal events, and cognitive-behavioral impairments, including mental delay of varying degrees. We conducted neurologic and neuroimaging examinations, as well as a neuropsychological assessment, of two men (22 and 30 years old) with mutations in the ATP1A3 gene (p.Leu757Pro and p.Val332Glu) who were experiencing typical AHC transient episodes of alternating weakness or paralysis in order to investigate causes of their poor social functioning. During neurologic examinations of both patients, which were performed between attacks, we observed involuntary movements such as chorea and upper-limb tremor. One patient also had dysarthria. Magnetic resonance imaging revealed no parenchymal brain lesions or atrophy in either patient. Neuropsychological examinations demonstrated near-normal (patient 1) or normal (patient 2) global cognitive functioning, with some isolated executive functioning deficits. Both patients had emotional and social dysfunction as well as difficulties adapting to normal adult life. Although the clinical presentation of AHC is usually dramatic, some patients have mild forms of the syndrome (eg, no significant intellectual disability). However, motor and movement disorders, as well as coexisting emotional-affective abnormalities, may affect these patients' ability to adapt to independent life.

Infantile-Onset Myelin Protein Zero-Related Demyelinating Neuropathy Presenting as an Upper Extremity Monoplegia.

We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene.

Modification of Cerebellar Afferent Pathway in the Subacute Phase of Stroke.

BACKGROUND: This study aims to identify the relationship between corticopontocerebellar tract (CPCT) and corticospinal tract (CST) integrity as well as motor function after stroke. MATERIALS AND METHODS: A total of 33 patients with stroke (18 left, 15 right hemispheric lesions) who underwent diffusion tensor imaging within 2 months of stroke onset and 17 age- and sex-matched healthy controls were retrospectively enrolled. Tract volume and the asymmetry index based on tract volume (AITV) of the CST and CPCT were used to identify structural changes in individual tracts and the correlation between those tracts. Motor function was assessed using the Medical Research Council (MRC) muscle scale, manual function test (MFT), functional ambulation category, and modified Barthel index. RESULTS: The volume of the affected CPCT was lower, and that of the unaffected CPCT was higher than the volumes in the control group (P < .001, P = .001, respectively). The CPCT AITV showed a strong positive correlation with the CST AITV in patients with either left or right hemispheric lesions (rs = .779, P < .001; rs = .732, P = .003, respectively). The CPCT AITV negatively correlated with the MRC muscle scale of the shoulder, wrist, and ankle muscles (r = -.490, -.490, -.416; P = .004, .004, .016, respectively). A higher unaffected CPCT volume was indicative of less affected upper extremity function, as assessed by MFT (rs = -.546, P = .029). CONCLUSIONS: Modification of the CPCT depended on CST integrity and was associated with the severity of hemiplegia and hemiplegic upper extremity function. The CPCT may complement the role of the CST and help to predict the motor function.