Changes In Basal Ganglia Research Articles

Reply: The cerebellum in Parkinson’s disease and parkinsonism in cerebellar disorders

ARTICLE Sir, We thank Pedroso et al. (2013) for their interest in our paper (Wu and Hallett, 2013), in which we discussed the role of the cerebellum in Parkinson’s disease; other types of parkinsonism were not included. Such parkinsonian disorders often contain overt pathological changes in both basal ganglia and cerebellar systems. The origin of these changes is generally thought to be primary in both locations, but it is conceivable that the primary pathology is in one location and secondary in the other. It is important to recognize that genetic mutations can cause different phenotypes and that the nomenclature …

EComment. Superior caval clamping without a cavoatrial shunt during bidirectional Glenn operation

We read with interest the paper by Mostafa et al. [1], in which they presented the results of two groups of single ventricle patients, who underwent bidirectional cavopulmonary anastomosis with and without a veno-atrial shunt. The authors indicate a mean venous pressure of 37.07 ± 7.12 mmHg in the non-shunted group for a mean clamp time of 9.85 ± 3.52 min. The mean intensive care unit stay was 2.57 ± 75 days in the non-shunted patients. The authors performed bidirectional Glenn operation in a cohort of patients aging between 8-108 months [1]. The superior vena cava carries at least half of the blood volume in the early periods of life [2,3]. With growth, the inferior vena cava dominates [3] and proportions become 1/3-4 in adulthood [2,3]. Thus, although superior vena cava clamping may be uneventful in later childhood or adulthood, clamping of the superior caval vein in the early periods of life may not be easily haemodynamically tolerated. The manoeuvre may lead to cardiac failure and an increased amount and number of inotropic agents may be required [2]. Moreover, although authors state the manoeuvre had not led to serious neurologic sequelae during clamping of the superior vena cava, intracerebral pressure increases and cerebral arterial flow diminishes for sure. The literature includes animal experiments of superior vena cava clamping in monkeys [4] and dogs [5]. Research indicates that temporary occlusion of the superior vena cava is safe, despite decreased cerebral blood flow during clamp application [4,5]. First of all, it seems that these experiments were performed on adult animals in both studies [4,5]. Moreover, Masuda et al. indicated histopathological changes in the basal ganglia, hippocampus and even bleeding at the frontal lobe in their experiments on monkeys [4]. Urayama et al. [5] experienced attenuated amplitudes of somatosensory evoked potentials and prolonged latency [5]. We never hesitate to perform cardiopulmonary bypass during bidirectional Glenn procedure at our institution. When an off-pump operation is planned, an external cavo-atrial shunt is created. Despite the shunt, at least 5 mcg/kg/min of dopamine facilitates the surgery. A cavo-atrial shunt with or without minimal dose of inotropic support during reconstruction of the bidirectional Glenn provides a non-adventurous procedure and is a safe technique to decompress the cerebral pressure, to minimize decrease in cerebral arterial blood flow and hence to prevent postoperative neurological events. The cannula inserted into the superior vena cava does not pose major trauma to the superior vena cava and usually does not cause venous distortion or even in case of doubt, the vein can be easily reconstructed. Conflict of interest: none declared.

Functional Imaging in Chronic Migraine

Chronic migraine is a relatively common disorder in neurological terms that causes very significant disability at a high cost. The precise mechanisms behind the progression of episodic migraine to chronic migraine are not well understood. Functional neuro-imaging works on the basis that neuronal activations are associated with changes in regional cerebral blood flow, and it can help us answer some of these questions. In this review, we discuss important recent studies in chronic migraine or studies relating to increasing frequency of migraine attacks. The findings show that increasing frequency of migraine attacks is associated with changes in key brainstem areas, basal ganglia and various cortical areas involved in pain.

Relationship between EEG Alpha3/Alpha2 Ratio and the Nucleus Accumbens in Subjects with Mild Cognitive Impairment

Background: The nucleus accumbens (NAc) has been associated with impulsive behavior in subjects with early cognitive impairment; grey matter (GM) changes of basal ganglia have been demonstrated to be involved in Alzheimer’s disease (AD). Moreover, the increase of EEG alpha3/alpha2 ratio has been associated with ADconverters subjects with mild cognitive impairment (MCI). Objective: To study the association of EEG marker with specific GM changes of NAc in subjects with MCI Methods: 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The alpha3/alpha2 ratio was computed for each subject. Three groups were obtained according to increasing tertiles values of alpha3/alpha2. Grey matter density differences between groups were investigated using a Voxel Based Morphometry technique. Results: Subjects with lower a3/a2 and middle a3/a2 ratio ratio showed greater gray matter reduction in the NAc bilaterally when compared to subjects with higher a3/a2 ratio. Conclusion: The a3/a2 ratio was associated with increase of grey matter density inside the NAc in MCI subjects at major risk to develop AD.

Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management.

Theta/Gamma EEG Frequency Ratio is Associated to Grey Matter Changes in Basal Ganglia in Subjects with Mild Cognitive Impairment

Background : grey matter (GM) changes of thalamus and basal ganglia have been demonstrated to be involved in dementia. Moreover, the increase of the EEG marker, theta/gamma ratio, has been associated with non-AD converters subjects with mild cognitive impairment (MCI). Objective : to study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to detect biomarkers (morpho-physiological) early predictive non-AD dementia. Methods : 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The theta/gamma ratio was computed for each subject. Three groups were obtained according to increasing tertiles values of theta/gamma ratio. Grey matter density differences between groups were investigated using a Voxel Based Morphometry technique. Results : subjects with higher theta/gamma ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio. Conclusion : The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Analysis of grey matter in thalamus and basal ganglia based on EEG α3/α2 frequency ratio reveals specific changes in subjects with mild cognitive impairment.

GM (grey matter) changes of thalamus and basal ganglia have been demonstrated to be involved in AD (Alzheimer's disease). Moreover, the increase of a specific EEG (electroencephalogram) marker, α3/α2, have been associated with AD-converters subjects with MCI (mild cognitive impairment). To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to detect biomarkers (morpho-physiological) early predictive of AD and non-AD dementia. Seventy-four adult subjects with MCI underwent EEG recording and high-resolution 3D MRI (three-dimensional magnetic resonance imaging). The α3/α2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of α3/α2 ratio. GM density differences between groups were investigated using a VBM (voxel-based morphometry) technique. Subjects with higher α3/α2 ratios when compared with subjects with lower and middle α3/α2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration

Biomarkers as indicators for the progression of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain still elusive. We performed a cross-sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV-infected patients. We enrolled 94 patients (82 men and 12 women; mean age 45±10years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho-tau, beta-amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF. We found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV-infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho-tau or A-beta-amyloid in CSF analysis. Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.

178. Interferon-alpha-induced fatigue is associated with alterations in CNS glutamate metabolism as measured by magnetic resonance spectroscopy

Peripheral inflammatory states and their behavioral consequences including fatigue have been well-documented. One mechanism that may contribute to inflammation-induced behavioral changes is alterations in central nervous system (CNS) glutamate metabolism. To examine the role of CNS glutamate in inflammation-induced fatigue, proton magnetic resonance spectroscopy ( MRS ) was conducted in 12 patients with hepatitis C (HCV) before and after 4 weeks of treatment with interferon ( IFN )- alpha compared to 12 HCV patients awaiting IFN-alpha therapy. IFN-alpha is an inflammatory cytokine well-known to induce symptoms of fatigue in a high percentage of patients. Compared to controls, the glutamate /creatine ratio in the left basal ganglia significantly increased following 4 weeks of IFN-alpha administration ( p < 0.05). This increase in the glutamate /creatine ratio was in turn significantly correlated with increases in fatigue severity ( r = 0.435, p = 0.034). Increased glutamate concentrations in the left basal ganglia are consistent with previously reported alterations in basal ganglia function following IFN-alpha treatment in cancer patients and patients with HCV. The data are also consistent with changes in basal ganglia function in healthy volunteers administered immune stimuli including endotoxin or typhoid vaccination. These data suggest that altered glutamate metabolism possibly as a result of altered glial function may contribute to basal ganglia changes following acute and chronic immune activation.

Disruption of striatal glutamatergic/GABAergic homeostasis following acute methamphetamine in mice

Methamphetamine leads to functional changes in basal ganglia that are linked to impairment in motor activity. Previous studies from our group and others have shown that a single high-methamphetamine injection induces striatal dopaminergic changes in rodents. However, striatal glutamatergic, GABAergic and serotoninergic changes remain elusive under this methamphetamine regimen. Moreover, nothing is known about the participation of the receptor for advanced glycation end-products (RAGE), which is overexpressed upon synaptic dysfunction and glial response, on methamphetamine-induced striatal dysfunction. The aim of this work was to provide an integrative characterization of the striatal changes in amino acids, monoamines and astroglia, as well as in the RAGE levels, and the associated motor activity profile of C57BL/6 adult mice, 72h after a single-high dose of methamphetamine (30mg/kg, i.p.). Our findings indicate, for the first time, that methamphetamine decreases striatal glutamine, glutamate and GABA levels, as well as glutamine/glutamate and GABA/glutamate ratios, while serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels remain unchanged. This methamphetamine regimen also produced dopaminergic terminal degeneration in the striatum, as evidenced by dopamine and tyrosine hydroxylase depletion. Consistently, methamphetamine decreased the locomotor activity of mice, in the open field test. In addition, increased levels of glutamine synthase and glial fibrillary acidic protein were observed. Nevertheless, methamphetamine failed to change RAGE levels. Our results show that acute methamphetamine intoxication induces pronounced changes in the striatal glutamatergic/GABAergic and dopaminergic homeostasis, along with astrocyte activation. These neurochemical and glial alterations are accompanied by impairment in locomotor activity.

A clinico‐radiological phenotype of voltage‐gated potassium channel complex antibody‐mediated disorder presenting with seizures and basal ganglia changes

In childhood, central nervous system (CNS) presentations associated with antibodies to voltage-gated potassium channel (VGKC) complex include limbic encephalitis, status epilepticus, epileptic encephalopathy, and autistic regression. We report the cases of two individuals (a 6-year-old male and an 11-year-old female) who presented with an acute-onset explosive seizure disorder with positive VGKC complex antibodies and bilateral basal ganglia changes on magnetic resonance imaging (MRI). Both patients made a complete clinical recovery, without immunotherapy, with resolution of the MRI changes and normalization of the antibody levels. Extended antibody testing, including testing for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein 2, and contactin-2 was negative. This could suggest that the clinico-radiological phenotype in our patients may in fact be associated with a novel autoreactive target(s) within the VGKC complex, as may be the case in other children with VGKC complex-mediated CNS disorders.

Differentiating symptomatic Parkin mutations carriers from patients with idiopathic Parkinson’s disease: Contribution of automated segmentation neuroimaging method

BackgroundParkin (PARK2) gene mutations are the predominant cause of autosomal recessive parkinsonism. Characteristic features include: early onset symptoms with slow clinical course, good response to low doses of levodopa, and frequently treatment-induced dyskinesia. Studies using a voxel-based morphometry approach showed a decrease in the gray matter volume of the basal ganglia in mutation carriers during the symptomatic stages. A bilateral, presumably compensatory increase of basal ganglia gray matter value was recently demonstrated in asymptomatic Parkin mutation carriers. Behavioral disorders including: anxiety, psychosis, panic attacks, depression, disturbed sexual, behavioral and obsessive–compulsive disorders have been reported in these patients. MethodA total of 28 Parkinson’s Disease (PD) patients consisting of 10 Young-Onset without Parkin mutations (YOPD), 9 Young-Onset with Parkin mutations (YOPD-p), 9 Late-Onset without Parkin mutations (LOPD) and 32 healthy control subjects were studied with an automated volumetric assessment method to quantify subcortical atrophy. Patients but not controls also underwent a neuropsychological and neuropsychiatric assessment. ResultsResults revealed a reduction of bilateral caudate nuclei volumes in YOPD-p patients compared to the YOPD patients while there were no statistically significant differences between other groups. YOPD-p patients showed similar results to other patient groups on neuropsychiatric and neuropsychological evaluation measures. ConclusionYOPD-p and YOPD patients showed a different pattern of volume changes in basal ganglia. Despite its relatively benign clinical course, carrying the Parkin mutation seems to be associated with greater atrophy in subcortical structures. Failure of compensatory mechanisms, different mutation types and pathophysiologic processes may underlie this diverse pattern of subcortical brain changes.

Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

In Parkinson's disease (PD), alteration of dopamine- (DA-) dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA) lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID). Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

A case of acute necrotizing encephalopathy associated with parainfluenza virus infection

Acute necrotizing encephalopathy (ANE) may be suspected when a young child presents with abrupt onset of altered mental status, seizures, or both. Definitive clinical diagnosis is based on magnetic resonance imaging (MRI) results. ANE is associated with influenza virus infections. Preliminary data suggests that up to 25% of ANE patients die, and up to 25% of ANE survivors develop substantial neurologic sequelae. Here, we describe a case of a comatose 22-month-old girl who was admitted to our hospital because of febrile illness and seizures. On day 13 of her illness, she died from ANE associated with infection from parainfluenza virus. Brain MRI results indicated diffuse bilateral symmetric signal changes in both basal ganglia, thalami, periventricular white matter, pons, and cerebral white matter, as well as generalized swelling of the brain.

EEG markers are associated to gray matter changes in thalamus and basal ganglia in subjects with mild cognitive impairment

Gray matter (GM) changes of thalamus and basal ganglia have been demonstrated to be involved in Alzheimer's disease (AD). Moreover, the increase of two EEG markers, alpha3/alpha2 and theta/gamma ratio, have been associated with, respectively, AD converter and non-AD converter subjects with mild cognitive impairment (MCI). To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to identify different MCI populations. 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The theta/gamma and alpha3/alpha2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of both alpha3/alpha2 and theta/gamma ratio. Gray matter density differences between groups were investigated using a voxel-based morphometry technique. Subjects with higher a3/a2 ratios when compared to subjects with lower and middle a3/a2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; subjects with higher t/g ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio. The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Dynamic susceptibility contrast-enhanced first-pass perfusion MR imaging in patients with subclinical hepatic encephalopathy

Subclinical hepatic encephalopathy (SHE) is frequently reported on single-photon emission computed tomography (SPECT), but is rarely described with magnetic resonance (MR) techniques. This study aimed to investigate hemodynamic changes in brain basal ganglia in patients with SHE using dynamic susceptibility contrast (DSC)-enhanced MR perfusion imaging. Twelve patients with SHE and ten age- and education-matched volunteers agreed to undergo MR examination. The scanning protocol included conventional anatomical images and DSC-enhanced perfusion MR imaging. Using MGH perfusion software, parameter maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were created. The bilateral caudate nucleus head, globus pallidus, putamen and thalamus were selected as regions of interest (ROI), with ipsilateral white matter of the frontal lobe used as reference. Ratios (ROI versus ipsilateral white matter in frontal lobe) for CBF, CBV and MTT in the patient group were compared with those in the control group. The CBF ratios for every ROI were higher in SHE patients versus the controls. Statistically, significant increases were detected in the left globus pallidus, putamen and thalamus (P<0.05). For MTT, the reduction in values reached statistical significance in the right head of the caudate nucleus and bilateral thalamus (P<0.05). CBV values were not significantly different compared with those of the control group (P>0.05). Increased CBF and decreased MTT values in the basal ganglia and thalamus were identified in patients with SHE. The CBF increase was compatible with the idea that the CBF is redistributed from cortical areas to the basal ganglia structures.

Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism

Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. Application of pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Furthermore, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. Thus, closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.

Sonographic Alteration of Lenticular Nucleus in Focal Task-Specific Dystonia of Musicians

Background/Aims: In distinct movement disorders, transcranial sonography detects alterations of deep brain structures with higher sensitivity than other neuroimaging methods. Lenticular nucleus hyperechogenicity on transcranial sonography, thought to be caused by increased local copper content, has been reported as a characteristic finding in primary spontaneous dystonia. Here, we wanted to find out whether deep brain structures are altered in task-specific dystonia. Methods: The frequency of sonographic brainstem and basal ganglia changes was studied in an investigator-blinded setting in 15 musicians with focal task-specific hand dystonia, 15 musicians without dystonia, and 15 age- and sex-matched nonmusicians without dystonia. Results: Lenticular nucleus hyperechogenicity was found in 12 musicians with task-specific dystonia, but only in 3 nondystonic musicians (Fisher’s exact test, p = 0.001) and 2 nonmusicians (p < 0.001). The degree of lenticular nucleus hyperechogenicity in affected musicians correlated with age, but not with duration of music practice or duration of dystonia. In 2 of 3 affected musicians with normal echogenic lenticular nucleus, substantia nigra hyperechogenicity was found. Conclusions: Our findings support the idea of a pathogenetic link between primary spontaneous and task-specific dystonia. Sonographic basal ganglia alteration might indicate a risk factor that in combination with extensive fine motor training promotes the manifestation of task-specific dystonia.

A model of healthy aging and motor inhibition in the basal ganglia

The basal ganglia have received a great deal of attention from modeling studies because of their putative role in normal motor function including action selection and sequencing, as well as their distubrances in Parkinson’s disease. However, their interaction is complex, and is thought to be more sophisticated than can be accounted for by simple box and plot diagrams. In the present study, we have examined trial by trial variations in response times in the stop signal task for both young (YA) and older (OA) adults. We compare previously reported YA data [1] with data collected from 18 older adults performing the same task. Unlike YA, the OA do not show a specific pattern of response times that is modulated by stop signal success in the previous trial. Additionally, the OA did not show an effect of inter trial interval (ITI) as was observed in YA. Based on our behavioral data [1], we concluded that a task switching interpretation was the most likely explanation of the YA results. We also compare the electrophysiological data collected during the ITI from OA and YA performing the stop signal task. In YA, the power spectral data revealed a midline frontal theta effect with more desynchronization following a stop signal trial. As in [1], we concluded that this evinced a task set switching interpretation as YA subjects went from a ‘ready to inhibit’ mode to a ‘ready to respond’ mode. In the OA data presented here, we failed to observe a similar frontal theta effect, which was expected given the lack of a behavioral result in the OA subjects. To test hypotheses about the role of the basal ganglia in task switching in young and older adults, we have developed a conductance-based network model of the subthalamic nucleus, internal and external segments of the globus pallidus. The model incorporates cellular properties described in previous modeling studies [3] based on experimental findings. First we establish network properties which lead to patterns of beta activity that are consistent with observed phenomenon in human subjects [2]. Next, we determine which network parameters affect trial to trial variations in response times within the model. Using this approach, we examine how known changes in healthy older adult basal ganglia may affect task performance. Similarly, we discuss the implications for Parkinson’s disease.

P21.9 Acquired toxoplasmosis as a rare cause of cerebellitis in immunocompetent child

primary influenzae A infection. Follow-up MR brain of both siblings showed bilateral atrophic changes of basal ganglia and marked cerebral atrophy. Follow-up CT brain showed bilateral basal ganglia calcifications over caudate nuclei and putamen. MECP2 duplication, nup62 and ARX gene mutations were negative. They did not response to Ldopa, biotin (5mg/kg/day) and pyridoxine. They are severely affected by their extrapyramidal symptoms, and had acquired microcephaly and severe global developmental delay. Conclusion: This report suggested a possible role of influenzae A in the pathomechanism of IBSN in a genetically predisposed family. In view of the phenotypic similarities between IBSN and BBGD, further assessment and comparison of these disorders and their responsiveness to biotin may reveal new information regarding the mechanism of striatal necrosis.