Bilateral Basal Ganglia Lesions Research Articles

SERAC1 Deficiency- A New Phenotype.

Introduction - SERAC1 deficiency phenotype range from MEGD(H)EL syndrome, the most severe, to juvenile complicated spastic paraplegia, to adult-onset dystonic features (in only one patient). The MEGD(H)EL syndrome is characterized by (3-methylglutaconic aciduria with deafness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome). Biochemical abnormalities: elevated urinary 3 - metilglutaconic and 3-metilglutaric acids, high lactate and alanine in serum. Diagnosis is confirmed when biallelic pathogenic variants in SERAC1 gene are found. Brain MRI: basal ganglia lesions and generalized atrophy. Results/Case report - A 30-year-old patient with a moderate intellectual disability, developed, since the age of 25, a progressive loss of previous capacities (hand dexterity, oral language), and later subacute generalized dystonic features. Currently he has spastic tetraparesis, dystonia, scoliosis and autistic behavior, with bilateral basal ganglia lesions on brain MRI. Genetic study revealed biallelic pathogenic variants in SERAC1 gene, confirm MEGD(H)EL. A 73 years old patient with cognitive impairment and progressive spastic tetraparesis had multiple periventricular T2 hyperintense lesions. She has a homozygotic SERAC1 variant NM_032861: exon4:c.T139A: p.F471 (rs112780453), considered benign. Biochemical study revealed elevated plasmatic alanine and urinary3-metilglutaconic and 3-metilglutaric acid. This profile is concordant with mitochondrial dysfunction and SERAC1 Deficit. Conclusion - The first patient has the clinical symptoms associated to the MEGD(H)EL syndrome, and the biochemical and genetic confirmation of the diagnosis, without reservations. However, in the second patient, the progressive paraparesis and cognitive impairment did not appear to be caused by multiple sclerosis nor subcortical vascular leukoencephalopathy (without vascular risk factors). The abnormal biochemical profile is suggestive of SERAC1 Deficiency, even without genetic confirmation. In what should we believe?

Encefalopatía e infarto del globus pallidum bilateral, secundarios a intoxicación con disulfiram. Reporte de caso pediátrico

El disulfiram (Antabuse®) es un fármaco que se usa ampliamente en pacientes con consumo crónico de alcohol, como parte del tratamiento del alcoholismo, con el fin de producir síntomas desagradables al mezclarse con etanol, por incremento de acetaldehído. Aunque se han descrito casos de intoxicación aun sin ingesta de alcohol con dosis terapéuticas y más comúnmente por sobredosis en adultos, son pocos los casos que se han descrito en niños.
 Se presenta a continuación el caso de un niño con intoxicación aguda por disulfiram, quien presentó en la fase aguda somnolencia que evolucionó a estupor; concomitantemente presentó crisis convulsivas, vómito, deshidratación, rigidez, temblor distal y diaforesis; al egreso, con secuelas neurológicas severas, caracterizadas por distonía bilateral y signos piramidales como resultado de lesión bilateral de los ganglios basales documentada por imagenología.

Partially reversible bilateral Lenticular fork sign and acute Parkinsonism in diabetic uremic syndrome (P5-11.005)

<h3>Objective:</h3> Not applicable <h3>Background:</h3> Diabetic uremic syndrome is a concept that has been increasingly recognized since it was proposed in 2003. It differs from uremic encephalopathy. Hereby, we describe the first case of North African Arab descent with end-stage renal disease and diabetes who developed acute Parkinsonism with bilateral lenticular fork sign and uremia that partially resolved after extensive dialysis therapy. <h3>Design/Methods:</h3> Not applicable <h3>Results:</h3> <h3>Case Description:</h3> 65 years old man with end-stage renal disease on peritoneal dialysis and newly diagnosed diabetes millets presented with a 3-day history of unsteady gait, generalized weakness, mild dysarthria, mild dysphagia, drowsiness, and changes in concentration. Examination revealed a mask face, dysphagia, absent gag reflex, dysphonia, generalized motor weakness more prominent in lower limbs, bradykinesia, absent knee reflexes, and myoclonic jerks. Laboratory studies showed urea 25 mmol/L, Creatinin 922 umol/L, arterial pH 7.25, and normal lactate. The lumbar puncture study was unremarkable. CT head showed swollen hypodense bilateral lentiform nuclei with a hypodense rim delineating the basal ganglia and giving the appearance of a lentiform fork sign. MRI showed bilateral T2 and FLAIR putamen and globus pallidus hyperintensity and significant lactate peak in the bilateral basal ganglia on MR spectroscopy. EMG study was evident of axonal polyneuropathy. IVIG course was commenced, and motor weakness improved. The peritoneal dialysis was intensified, and later treatment was switched to hemodialysis. Acidemia resolved, and uremia significantly improved. Two weeks post-admission, the fork sign on MRI significantly regressed, and the patient’s Parkinsonian symptoms partially improved. <h3>Conclusions:</h3> Development of acute or subacute extrapyramidal movement disorder in end-stage renal disease associated with diabetes should promote the possibility of diabetic uremic syndrome with bilateral basal ganglia lesions forming fork sign appearance that occurs early on brain imaging. Usually, extensive dialysis, preferable hemodialysis, leads to a total resolution of brain imaging and partial resolution of clinical findings. <b>Disclosure:</b> Dr. Nofal has nothing to disclose. Dr. Noorain has nothing to disclose. Dr. Safan has nothing to disclose. Dr. Adeli has nothing to disclose. Dr. Sokrab has nothing to disclose.

Clinical Reasoning: A 14-Year-Old Girl With Reversible Peripheral Neuropathy and Encephalopathy.

A 14-year-old girl presented with acute ascending, symmetric numbness and flaccid paralysis three weeks after a suspected gastrointestinal infection. She had experienced anorexia since this gastrointestinal episode. EMG showed a sensorimotor axonal polyneuropathy. Routine CSF analysis and serum-specific antibodies (anti-ganglioside and node of Ranvier-associated antibodies) were all negative. Laboratory investigations for possible etiologies only revealed mild metabolic perturbations. During her hospitalization, she developed mild cognitive deficits. Brain MRI showed bilateral symmetric basal ganglia lesions with hyperintensity on T2-FLAIR, DWI hyperintensity and corresponding ADC hypointensity, but without contrast enhancement. A more thorough and detailed history indicated exercise intolerance, and specific examinations subsequently revealed an underlying etiology. This case presentation discusses specific etiology of an acute-onset, diffuse and symmetric neuropathy after an acquired injury in a teenager, emphasizing the need of a broad differential diagnosis in this condition.

Anti‐metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review

To describe the clinical and radiological characteristics of anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis. We reviewed the clinical data of five patients with anti-mGluR5 encephalitis, and performed a literature review. The five cases included a 52-year-old man who developed a biphasic course of anti-mGluR5 encephalitis after herpes simplex encephalitis, a 22-year-old woman who showed bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI), and a 36-year-old man with mixed aphasia and generalized tonic-clonic seizures, a 51-year-old man presented with personality changes, hallucinations, delusions, sleeping disorders and a 58-year-old man with short-term memory deficits and absence seizures.. There are 16 reported cases of anti-mGluR5 encephalitis worldwide. Of all 21 patients, with a median onset age of 35 years old, the main neurological symptoms were cognitive impairment (85.7%, 18/21), psychiatric or behavior problems (76.2%, 16/21), seizures (57.1%, 12/21), sleeping disorders (52.4%, 11/21), different degrees of decreased consciousness (42.9%, 9/21), and movement disorders (23.8%, 5/21). Brain MRI was normal in 11 of 21 patients. Lesions of the limbic lobes were presented in 5 patients, while involvement of other extralimbic regions was also reported. Seven of 21 (33.3%) cases were combined with tumors. Elevated white blood cell counts or specific oligoclonal IgG bands in the cerebrospinal fluid were found in 18 of 21 patients, with marked improvements observed after immunotherapy. Patients with anti-mGluR5 encephalitis typically present with diffuse, rather than purely limbic, encephalitis. Anti-mGluR5 encephalitis can be triggered by herpes simplex encephalitis. The risk of a combined tumor may be reduced in anti-mGluR5 encephalitis patients.

Psychopathological network for early-onset post-stroke depression symptoms

BackgroundPost-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD.MethodsA total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data werecollected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity.ResultsDepressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region.ConclusionsThere are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDSseverity.Trial registrationURL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

Wernicke-Korsakoff Syndrome in a Young Adult on Dialysis Who Showed Bilateral Ganglia Lesions: A Case Report.

A 30-year-old man admitted with renal dysfunction (serum creatinine, 8.19 mg/dL) was diagnosed with immunoglobulin A nephritis through a renal biopsy. He was treated with intravenous methylprednisolone pulse therapy and urgent hemodialysis, and eventually, he underwent maintenance hemodialysis. On day 108, he developed amnesia. Magnetic resonance imaging revealed bilateral basal ganglia lesions. Wernicke encephalopathy (WE) was diagnosed based on decreased serum thiamine concentration (12.8 μg/dL; reference range, 24-66 μg/dL). Thiamine replacement therapy was initiated, but the Wernicke-Korsakoff syndrome persisted. Careful monitoring of thiamine is required in patients undergoing dialysis. In addition, patients with WE may exhibit bilateral basal ganglia lesions.

Teaching NeuroImage: Human Encephalitis Caused by Pseudorabies Virus Infection.

A 51-year-old woman presented with fever and loss of consciousness for 4 days. Images showed symmetrical lesions in bilateral cortex, limbic system, and basal ganglia (Figure). CSF analysis suggested viral infection. Next-generation sequencing identified 349 unique sequence reads for pseudorabies virus (PRV). She was diagnosed with PRV encephalitis. Epidemiologic survey revealed she was a pork dealer. PRV, also called Suid herpesvirus-1, primarily infects swine. It is reported that PRV can cause human infection through infected swine or pork.1,2 This case suggests unexplained severe encephalitis with similar MRI, and a history of relevant exposure should consider the possibility of PRV infection.

Movement Disorders Resulting From Bilateral Basal Ganglia Lesions in End-Stage Kidney Disease: A Systematic Review

Objective The basal ganglia (BG) are susceptible to fluctuations in blood urea levels, sometimes resulting in movement disorders. We described patients with end-stage kidney disease (ESKD) presenting with movement disorders associated with bilateral BG lesions on imaging.Methods We report four patients and systematically reviewed all published cases of ESKD presenting with movement disorders and bilateral BG lesions (EBSCOhost and Ovid).Results Of the 72 patients identified, 55 (76.4%) were on regular dialysis. Parkinsonism was the most common movement disorder (n = 39; 54.2%), followed by chorea (n = 24; 33.3%). Diabetes mellitus (n = 51; 70.8%) and hypertension (n = 16; 22.2%) were the most common risk factors. Forty-three (59.7%) were of Asian ethnicity. Complete clinical resolution was reported in 17 (30.9%) patients, while 38 (69.1%) had incomplete clinical resolution with relapse. Complete radiological resolution occurred in 14 (34.1%) patients.Conclusion Movement disorders associated with BG lesions should be recognized as a rare and potentially reversible metabolic movement disorder in patients with ESKD.

Severe Fever with Thrombocytopenia Syndrome Presenting with Bilateral Basal Ganglia Lesions

Severe Fever with Thrombocytopenia Syndrome Presenting with Bilateral Basal Ganglia Lesions

Genetic diagnosis of basal ganglia disease in childhood.

To correlate clinical, radiological, and biochemical features with genetic findings in children with bilateral basal ganglia lesions of unknown aetiology, and propose a diagnostic algorithm for early recognition. Children with basal ganglia disease were recruited in a 2-year prospective multicentre study for clinical, biomarker, and genetic studies. Radiological pattern recognition was examined by hierarchical clustering analysis. We identified 22 genetic conditions in 30 out of 62 paediatric patients (37 males, 25females; mean age at onset 2y, SD 3; range 0-10y; mean age at assessment 11y, range 1-25y) through gene panels (n=11), whole-exome sequencing (n=13), and mitochondrial DNA (mtDNA) sequencing (n=6). Genetic aetiologies included mitochondrial diseases (57%), Aicardi-Goutières syndrome (20%), and monogenic causes of dystonia and/or epilepsy (17%) mimicking Leigh syndrome. Radiological abnormalities included T2-hyperintense lesions (n=26) and lesions caused by calcium or manganese mineralization (n=9). Three clusters were identified: the pallidal, neostriatal, and striatal, plus the last including mtDNA defects in the oxidative phosphorylation system with prominent brain atrophy. Mitochondrial biomarkers showed poor sensitivity and specificity in children with mitochondrial disease, whereas interferon signature was observed in all patients with patients with Aicardi-Goutières syndrome. Combined whole-exome and mtDNA sequencing allowed the identification of several genetic conditions affecting basal ganglia metabolism. We propose a diagnostic algorithm which prioritizes early use of next-generation sequencing on the basis of three clusters of basal ganglia lesions.

Autoimmune basal ganglia encephalitis associated with anti-recoverin antibodies: A case report

Autoimmune basal ganglia encephalitis causes neurological symptoms such as parkinsonism associated with basal ganglia lesions. Here, we report a case of autoimmune basal ganglia encephalitis without retinal lesions or malignancy harboring anti-recoverin antibodies. The patient was a 67-year-old Japanese woman who developed anorexia, parkinsonism, and disturbance of consciousness 7 days before admission. Brain magnetic resonance imaging showed hyperintense bilateral basal ganglia lesions on fluid-attenuated inversion recovery images. 18F-fluorodeoxyglucose-positron emission tomography showed no malignancy in the trunk, and dopamine transporter single-photon emission computed tomography with dopamine transporters revealed reduced radiotracer uptake in the basal ganglia. Further, anti-recoverin IgG antibodies were detected in serum immunoblot. Based on the clinical and imaging findings, the patient was diagnosed with autoimmune basal ganglia encephalitis with anti-recoverin antibodies and administered high-dose immunoglobulins (HD-IVIG), which led to an improvement in clinical symptoms. Anti-recoverin antibodies are paraneoplastic antibodies that explicitly bind to Ca2+-binding proteins in the retina and cause retinopathy. This pathological sequence is defined as cancer-associated retinopathy (CAR). However, in our case, autoimmune basal ganglia encephalitis developed without CAR syndrome or malignancy. Clinicians should be aware of the possibility of autoimmune basal ganglia encephalitis showing anti-recoverin antibodies but no CAR syndrome or malignancy, which should be treated with HD-IVIG therapy.

Acute Onset Chorea in Profound Hypophosphatemia with Bilateral Basal Ganglia Lesions (2898)

Acute Onset Chorea in Profound Hypophosphatemia with Bilateral Basal Ganglia Lesions (2898)

Syndrome of uremic encephalopathy and bilateral basal ganglia lesions in non-diabetic hemodialysis patient: a case report

BackgroundUremic encephalopathy (UE), a toxic metabolic encephalopathy, is an uncommon complication resulting from endogenous uremic toxins in patients with severe renal failure. UE syndrome can range from mild inattention to coma. The imaging findings of UE include cortical or subcortical involvement, basal ganglia involvement and white matter involvement. The basal ganglia type is uncommon, although previous cases have reported that Asian patients with diabetes mellitus (DM) are usually affected.Case presentationA 32 year-old woman with a history of non-diabetic hemodialysis for 3 years suffered from severe involuntary movement, and brain magnetic resonance imaging showed symmetrical T2-weighted imaging (T2WI) and T2/fluid-attenuated inversion recovery (T2FLAIR) hyperintense nonhemorrhagic lesions in the bilateral basal ganglia. She was diagnosed with UE as syndrome of bilateral basal ganglia lesions, due to a combined effect of uremic toxins and hyperthyroidism. After treatment with high frequency and high flux dialysis, hyperbaric oxygen therapy and declining parathyroid hormone, the patient achieved complete remission with normal body movement and was discharged.ConclusionUE with basal ganglia involvement is uncommon, although generally seen in Asian patients with DM. Our case reported a hemodialysis patient that had non-diabetic UE with typical bilateral basal ganglia lesions, presenting with involuntary movement.

Neurofibromatosis typeⅠmanifested as early-onset epileptic encephalopathy and bilateral basal ganglia lesions

Neurofibromatosis typeⅠmanifested as early-onset epileptic encephalopathy and bilateral basal ganglia lesions

Primary progressive freezing gait with bilateral basal ganglia lesion in a uremic patient

Primary progressive freezing gait with bilateral basal ganglia lesion in a uremic patient

Impairment of astrocytic glutaminolysis in glutaric aciduria type I.

Glutaric aciduria type I is a rare, autosomal recessive, inherited defect of glutaryl-CoA dehydrogenase. Deficiency of this protein in L-lysine degradation leads to the characteristic accumulation of nontoxic glutarylcarnitine and neurotoxic glutaric acid (GA), glutaryl-CoA, and 3-hydroxyglutaric acid. Untreated patients develop bilateral lesions of basal ganglia resulting in a complex movement disorder with predominant dystonia in infancy and early childhood. The current pathomechanistic concept strongly focuses on imbalanced neuronal energy metabolism due to accumulating metabolites, whereas little is known about the pathomechanistic role of astrocytes, which are thought to be in constant metabolic crosstalk with neurons. We found that glutaric acid (GA) causes astrocytic cell death under starvation cell culture conditions, i.e. low glucose, without glutamine and fetal calf serum. Glutamine completely abolished GA-induced toxicity, suggesting involvement of glutaminolysis. Increasing dependence on glutaminolysis by chemical induction of hypoxia signaling-potentiated GA-induced toxicity. We further show that GA disturbs glutamine degradation by specifically inhibiting glutamate dehydrogenase. Summarizing our study shows that pathologically relevant concentrations of GA block an important step in the metabolic crosstalk between neurons and astrocytes, ultimately leading to astrocytic cell death.

Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature

BackgroundLeigh syndrome is an early-onset progressive neurodegenerative disorder typically involving lesions of the bilateral basal ganglia, thalami, and brainstem. Isolated involvement of the cerebellum is uncommon. Patient DescriptionWe present a six-year-old boy with Leigh syndrome who presented with recurrent episodes of ataxia and dysarthria. He was diagnosed with Leigh syndrome at two years of age with bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI). Genetic testing confirmed a diagnosis of Leigh syndrome secondary to a homoplasmic mitochondrial DNA mutation (m.9176T>C). He experienced regressive episodes (ages five and six years). Each regressive episode had a similar presentation with worsening of baseline ataxia and dysarthria. The first episode mimicked infectious cerebellitis, with elevated cerebral spinal fluid (CSF) protein and white blood cell count. No organisms were isolated from the CSF/blood during any of the regressive episodes. Brain MRI consistently showed cerebellar lesions, however cerebellar spectroscopy during the second episode found an elevated lactate peak, a decrease of the N-acetylaspartate peak, and elevation of the choline peak; consistent with an acute exacerbation of Leigh syndrome. ConclusionsLeigh syndrome can present primarily with involvement of the cerebellum, and it should be considered in the differential diagnosis for acute cerebellitis

Amnesia Associated with Bilateral Hippocampal and Bilateral Basal Ganglia Lesions in Anoxia with Stimulant Use

We report a case of a 55-year-old man with ischemic lesions of the bilateral hippocampus and bilateral basal ganglia following a myocardial infarction during an episode of multiple drug use with subsequent anoxia requiring resuscitation. He presented for a neuropsychological evaluation with an anterograde amnesia for both explicit and procedural memory. There are two main points to this case, the unique aspects of the bilateral multifocal lesions and the functional, cognitive impact of these lesions. We hypothesize that his rare focal bilateral lesions of both the hippocampus and basal ganglia are a result of anoxia acting in synergy with his stimulant drug use (cocaine and/or 3,4-methylenedioxy-methamphetamine). Second, his unique lesions produced an explicit and implicit/procedural anterograde amnesia.

Leber's Hereditary Optic Neuropathy Associated with the m.10197G&gt;A Mutation

Leber hereditary optic neuropathy (LHON) is an optic neuropathy caused by homoplasmic or heteroplasmic mtDNA mutations, which predominantly cause damage to the retinal ganglion cells (RGCs). The mtND3*10197A (m.10197G>A) mutation has been identified as the novel causative gene in Chinese patients with LHON and dystonia [1]. The m.10197G>A mutation also has been detected in patients with bilateral basal ganglia lesions and Leigh syndrome [2-4]. This mutation substitutes a threonine for an alanine at codon 47 of MTND3.