MELAS Missed for Years: Stroke-Like Lesions Are No Indication for Brain Biopsy

A 56-year-old female with a history of chronic alcoholism until age 38 y with a relapse between ages 45 and 46 y developed seizures, psychosis, and hemianopia to the left at age 46 y. Imaging revealed a right parieto-occipital lesion with intralesional bleeding. Five months after the first lesion she developed a second left parieto-occipital lesion, resulting in cortical blindness. Extensive workup, including brain biopsy, was noninformative. Retrospectively, the occipital abnormalities were identified as stroke-like lesions (SLLs). Further manifestations of the mitochondrial disorder (MID) were tremor, cerebral atrophy, bilateral basal ganglia, calcification, glaucoma, hypoacusis, short stature, hyperostosis frontalis, hyperthyroidism, sick-sinus syndrome and AV-block-1, and myopathy. According to the Walker criteria, a possible MID was diagnosed. In conclusion, adult-onset MID may be missed for years, SLLs may be easily misinterpreted entailing brain biopsy, and psychosis may contribute to a reduced impact for proper workup of a MID.

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MITOCHONDRIAL CYTOPATHY PRESENTING WITH CEREBELLAR ATAXIA

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.73 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.166-e4

Author(s):

Emily Pegg ◽

Katherine Dodd ◽

Sandip Shaunak

Keyword(s):

Family History ◽

Cerebellar Ataxia ◽

Fragile X ◽

Mitochondrial Disorder ◽

Cerebral Atrophy ◽

Oligoclonal Bands ◽

Spinocerebellar Ataxias ◽

Antineuronal Antibodies ◽

Mitochondrial Cytopathy ◽

History Of

A previously fit and well 59 year old man presented with a 3 year history of slowly progressive decline in mobility with increasing unsteadiness and falls. He also reported clumsiness of both hands and his wife noted poor memory. There was no family history of note, including deafness and diabetes. He drank alcohol occasionally. On examination he had signs consistent with a cerebellar and pyramidal syndrome with subcortical cognitive impairment.An MRI scan of the brain and spine showed significant generalised cerebral atrophy. CSF protein was 0.80g/L, with normal cell count and no oligoclonal bands. Blood tests were normal or negative for antineuronal antibodies, vitamin E, coeliac disease, autoimmune screen. Genetic tests for spinocerebellar ataxias, Freidreich's, fragile X syndrome and DRPLA were also negative. Muscle biopsy revealed mitochondrial aggregation with COX negative fibres, in keeping with a mitochondrial disorder. Genetic testing found a novel mtDNA variant (p.GLY46Asp) at low levels within the MT-CO3 gene.He has subsequently developed myoclonus and generalised tonic clonic seizures but there is no evidence of other system involvement.Mitochondrial disorders should be considered in the differential diagnosis of cerebellar ataxia, even in the absence of multisystem involvement or a significant family history.

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038 Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia mimicking systemic lupus erythematosus cerebral vasculitis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.37 ◽

2018 ◽

Vol 89 (6) ◽

pp. A16.1-A16

Author(s):

Michal Lubomski ◽

Michael Buckland ◽

Joanne Sy ◽

Heng Wei ◽

Irene Tan ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

White Matter ◽

Lupus Erythematosus ◽

Positive Family History ◽

Brain Biopsy ◽

Cerebral Vasculitis ◽

Adult Onset ◽

Systemic Lupus ◽

Cerebral Mri ◽

History Of

IntroductionWe present an unusual case of adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP) mimicking systemic lupus erythematosus (SLE) cerebral vasculitis. ALSP is an autosomal dominant progressive leukodystrophy, associated with mutations in the CSF1R gene, which induce dysregulation of microglia. The case was compiled from records of clinical data, imaging, brain biopsy and genetic studies.CaseA 56 year old previously high functioning man of Southern Chinese origin was hospitalised with recurrent seizures. He had a prior 4 year history of progressive neuropsychiatric features, and 1 year of cognitive decline and occasional falls. Within the year prior, he had positive SLE serology and a renal biopsy consistent with lupus nephritis treated with steroids, mycophenolate, hydroxyl-chloroquine, and later rituximab due to concerns of evolving cerebral vasculitis on cerebral MRI and SPECT scan with MoCA of 20/30. Examination after seizure therapy revealed hyperreflexia, fine tremor, myoclonus, pseudobulbar affect, ideomotor apraxia and slow, independent gait. RUDAS was 6/30 with perseveration. CSF examination and SLE serology were quiescent. Consecutive brain MRIs showed multiple regions of worsening high T2/FLAIR signal in the corpus callosum and supra-tentorial white matter with persistent restricted diffusion. IV steroids and cyclophosphamide were added. Following treatment unresponsiveness, a frontal lobe brain biopsy demonstrated white matter gliosis with prominent axonal spheroids consistent with a primary leukoencephalopathy, with no inflammation, vasculitis nor infection. Immunotherapy was weaned. Genetic testing confirmed a positive CSF1R mutation (c.2329C>T; p. Arg777Trp in Exon 18). A positive family history of dementia in the patient’s elderly mother overseas was identified. The patient remained mobile but mute, and fatally aspirated 8 months after final presentation.ConclusionThis report illustrates an unusual presentation of ALSP, initially misdiagnosed as SLE vasculitis. Clinicians should consider an adult onset leukodystrophy and proceed to biopsy and CSF1R gene testing early in suspected ‘refractory cerebral vasculitis’.

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Transient complete AV block during transcatheter ablation of a left posteroseptal anomalous pathway in a patient with previous history of ventricular septal defect patch closure

EP Europace ◽

10.1016/s1099-5129(01)80389-5 ◽

2001 ◽

Vol 2 ◽

pp. A98-A98

Keyword(s):

Ventricular Septal Defect ◽

Septal Defect ◽

Previous History ◽

Av Block ◽

History Of ◽

Patch Closure ◽

Complete Av Block

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Disease-associated HCN4 V759I variant is not sufficient to impair cardiac pacemaking

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-020-02481-3 ◽

2020 ◽

Vol 472 (12) ◽

pp. 1733-1742

Author(s):

Nadine Erlenhardt ◽

Olaf Kletke ◽

Franziska Wohlfarth ◽

Marlene A. Komadowski ◽

Lukas Clasen ◽

...

Keyword(s):

Family History ◽

Sick Sinus Syndrome ◽

Cardiac Pacemaker ◽

Cell Surface Expression ◽

Pacemaker Activity ◽

Hcn Channel ◽

Functional Interpretation ◽

Rat Cardiomyocytes ◽

Cardiac Pacemaking ◽

History Of

AbstractThe hyperpolarization-activated cation current If is a key determinant for cardiac pacemaker activity. It is conducted by subunits of the hyperpolarization-activated cyclic nucleotide–gated (HCN) channel family, of which HCN4 is predominant in mammalian heart. Both loss-of-function and gain-of-function mutations of the HCN4 gene are associated with sinus node dysfunction in humans; however, their functional impact is not fully understood yet. Here, we sought to characterize a HCN4 V759I variant detected in a patient with a family history of sick sinus syndrome. The genomic analysis yielded a mono-allelic HCN4 V759I variant in a 49-year-old woman presenting with a family history of sick sinus syndrome. This HCN4 variant was previously classified as putatively pathogenic because genetically linked to sudden infant death syndrome and malignant epilepsy. However, detailed electrophysiological and cell biological characterization of HCN4 V759I in Xenopus laevis oocytes and embryonic rat cardiomyocytes, respectively, did not reveal any obvious abnormality. Voltage dependence and kinetics of mutant channel activation, modulation of cAMP-gating by the neuronal HCN channel auxiliary subunit PEX5R, and cell surface expression were indistinguishable from wild-type HCN4. In good agreement, the clinically likewise affected mother of the patient does not exhibit the reported HCN4 variance. HCN4 V759I resembles an innocuous genetic HCN channel variant, which is not sufficient to disturb cardiac pacemaking. Once more, our work emphasizes the importance of careful functional interpretation of genetic findings not only in the context of hereditary cardiac arrhythmias.

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Susac's Syndrome

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100011549 ◽

2011 ◽

Vol 38 (2) ◽

pp. 335-337 ◽

Cited By ~ 3

Author(s):

Kevin Lian ◽

Rekha Siripurapu ◽

Robert Yeung ◽

Julia Hopyan ◽

Kenneth T. Eng ◽

...

Keyword(s):

Corpus Callosum ◽

White Matter Hyperintensities ◽

Brain Biopsy ◽

High Dose ◽

Normal Brain ◽

Left Hand ◽

Elevated Protein ◽

Fluid Attenuated Inversion Recovery ◽

History Of ◽

Previous Medical History

A 40-year-old woman with no significant previous medical history presented with a three month history of ataxia, confusion, memory difficulties, and headaches. Physical examination revealed numbness in the left hand, but was otherwise unremarkable. Magnetic resonance imaging fluid-attenuated inversion recovery (MRI FLAIR) images demonstrated multiple small white matter hyperintensities, including lesions involving the corpus callosum. There were also deep gray nuclei lesions (Figure 1). The corpus callosum lesions involved the central fibers (Figure 2). Post gadolinium T1 images demonstrated enhancement of some of the lesions as well as extensive perivascular and leptomeningeal enhancement (Figure 3). Extensive infectious serology, autoimmune panel, and paraneoplastic antibodies were negative. Lumbar puncture revealed elevated protein (1116 mg/L), but was otherwise normal. Brain biopsy indicated no apparent pathology. The patient was tentatively diagnosed with acute encephalopathy and treated with high dose steroids seven days after presentation. She was subsequently discharged and was sent for rehabilitation.

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Adult neuronal ceroid lipofuscinosis with clinical findings consistent with a butterfly glioma

Journal of Neurosurgery ◽

10.3171/jns.1998.88.2.0314 ◽

1998 ◽

Vol 88 (2) ◽

pp. 314-318 ◽

Cited By ~ 6

Author(s):

Stefanie Hammersen ◽

Mario Brock ◽

Jorge Cervós-Navarro

Keyword(s):

Muscular Atrophy ◽

Neuronal Ceroid Lipofuscinosis ◽

Cerebral Atrophy ◽

Brain Biopsy ◽

Progressive Dementia ◽

Ataxic Gait ◽

Content Type ◽

Presenting Symptoms ◽

Ceroid Lipofuscinosis ◽

Kufs Disease

✓ The authors report a case of neuronal ceroid lipofuscinosis (Kufs' disease) confirmed by stereotactically obtained brain biopsy findings and initially diagnosed as a butterfly glioma. The presenting symptoms in the 64-year-old patient were mental alterations with progressive dementia, followed by muscular atrophy and myoclonia with distal preponderance. The mild initial disturbances of coordination increased, and the patient developed a markedly ataxic gait. Computerized tomography (CT) scanning and magnetic resonance imaging revealed generalized cerebral atrophy and a bifrontal space-occupying lesion involving the callosum. The original “clearcut” diagnosis of glioblastoma multiforme, based on CT scans, was unexpectedly disproved by examination of stereotactically obtained brain biopsy specimens, which revealed a neuronal ceroid lipofuscinosis (Kufs' disease). To the authors' knowledge, this is the first report of a case presenting with both diffuse brain atrophy and localized accumulation of neuronal lipofuscin, mimicking a mass lesion on radiological studies.

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Huntington`s Chorea - a Case Report and review of literature

Annals of King Edward Medical University ◽

10.21649/akemu.v9i4.1356 ◽

2016 ◽

Vol 9 (4) ◽

Author(s):

Muhammad Afzal ◽

Anjum Iqbal ◽

Nadeem Azam ◽

Koukab Javed ◽

Ghana Shahid

Keyword(s):

Serum Alkaline Phosphatase ◽

Cerebral Atrophy ◽

Serum Copper ◽

The Body ◽

Early Dementia ◽

Similar Disease ◽

History Of ◽

Eye Examination ◽

Laboratory Investigations ◽

Naval Hospital

A 45 years old gentleman presented to Medical Clinic of Naval Hospital (PNS Hafeez) Islamabad in January 2001 with choreform movements of the body and early dementia of six months duration. He had a strong family history of similar disease, which included his father and two brothers. On neurological examination he had choreoathetoid movements and features of early dementia. His chest was clinically clear and examination of heart and abdomen was normal. Eye examination did not reveal any evidence of Kayser-Fleischer rings (seen in Wilson`s disease). Laboratory investigations showed haemoglobin 13.8 Gm/dl, WBC 7.7 x10e9/L, serum urea 32 mg/dl, serum sodium 139 mmol/L serum potassium 3.8 mmol/L, ASO titre less than 200 IU/ml, serum bilirubin 6 umol/L, ALT 102 U/L, serum alkaline phosphatase 155 U/L, serum caeruloplasmin 42 mg/dl and serum copper 164 mmol/L (WNL). X-ray chest was normal and CT scan brain showed early generalized cerebral atrophy. He was managed with haloperidol (0.5mg) 12 hourly, Procyclidine (kemadrin, 5mg) 8 hourly and Propranolol (Inderal 10mg) 8 hourly. He was discharged from hospital with relative improvement after 2 weeks.

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Clinical, epidemiological and autoimmune associations in childhood vitiligo in Qatar

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20200594 ◽

2020 ◽

Vol 6 (2) ◽

pp. 151

Author(s):

Haya Al Mannai ◽

Mohamed Allam ◽

Hassan Riad

Keyword(s):

Family History ◽

Autoimmune Diseases ◽

Age Of Onset ◽

Positive Family History ◽

Thyroid Peroxidase ◽

Base Line ◽

Adult Onset ◽

Prognostic Features ◽

History Of ◽

The Mean

Background: Childhood vitiligo although clinically similar to adult onset vitiligo but it has distinct clinical, epidemiological and prognostic features compared to adult onset vitiligo.Methods: This is a retrospective study that was carried out on 85 pediatric patients up to age of 18 years old with the diagnosis of vitiligo, where the clinical and epidemiological data including clinical type of vitiligo, family history of autoimmune diseases like thyroid disorders and diabetes mellitus and laboratory results including anti-thyroid peroxidase antibodies (anti-TPO antibodies), anti-parietal cell antibodies, antinuclear antibodies (ANA), Vitamin D and Vitamin B12 were retrieved from the files of these patients.Results: The mean age of the children affected by vitiligo was 10.4 years, the mean age of onset of vitiligo was 5.4 years, 54 (63.5%) percent were girls and 31 (36.5%) were boys. A positive family history of vitiligo was found in 44.7% of the participants, family history of DM was found in 64.7% of patients and family history of thyroid disease was found in 32.9% of the participants. The prevalence of thyroid autoimmunity was found to be in 22.4% of total participants.Conclusions: Childhood vitiligo has distinct clinical features, more common family history for autoimmune diseases and thyroid autoantibodies rather than overt clinical diseases, which raise the necessity to perform a routine initial immunological and thyroid screening in children with vitiligo and to repeat them at annual bases if there were abnormal values at base line or strong family history.

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THE ROLE OF HIV IN THE PATHOGENESIS OF ADULT-ONSET VERNAL KERATOCONJUNCTIVITIS: A DEMOGRAPHIC AND EPIDEMIOLOGICAL STUDY

10.21203/rs.2.324/v1 ◽

2019 ◽

Author(s):

Anine Kritzinger ◽

Anthony Grant Zaborowski ◽

Wilbert Sibanda ◽

Linda Visser

Keyword(s):

Cd4 Count ◽

Vernal Keratoconjunctivitis ◽

Hiv Positive ◽

P Value ◽

Adult Onset ◽

Atopic Diseases ◽

Hiv Status ◽

Chi Squared ◽

History Of ◽

New Onset

Abstract Background: Very few studies in the literature describe adult-onset vernal keratoconjunctivitis (VKC). HIV has many associated ocular pathologies and an association with VKC has not been described yet. The aim is to identify and describe patients who present with new-onset VKC after puberty, with no prior history of atopic diseases or allergies. Methods: The study consisted of two parts: the first part was a prospective observational descriptive study of patients with adult-onset VKC, detailing the epidemiological and demographic characteristics of these patients, including their HIV status. The second was a case-control study to determine the relationship of a CD4 count with adult-onset VKC in the setting of HIV. Patients were recruited between January 2016 and November 2017 from McCord Provincial Eye hospital, one of two large referral hospitals for the province of KwaZulu-Natal, South Africa. Patients presenting to the Eye clinic were screened at the Primary Eye Care Unit. Inclusion criteria were age 15 years and older with signs and symptoms of new-onset VKC. Exclusion criteria were a history of childhood atopic diseases, atopic keratoconjunctivitis and patients who refused HIV testing. Data collected included HIV status, CD4 count where appropriate, anti-nuclear antibodies and total serum immunoglobulin E. Results: 33 patients were included in this study; females n=16, males n=17. The mean age at presentation was 32.45±9.93 years, 95% CI=28.94-35.97. All of the patients were black Africans. One patient tested ANA positive. 51.5% of patients had a raised IgE level. A total of 13 of 25 HIV positive patients (52%) had a raised IgE. The proportion of HIV positive patients was statistically different from the HIV negative group, with Chi-squared = 21.866, p-value <0.0001. 72% of the HIV positive patients were grouped as immunodeficient according to their CD4 counts. An association was proven between severely immunodeficient patients and the risk of having VKC (chi-squared=4.992, p-value=0.0255). Conclusion: In this cohort a statistically significant association was found between adult-onset vernal keratoconjunctivitis and an HIV positive status. This association calls for more research on the subject, but could imply that patients presenting with adult-onset VKC should be offered an HIV test. Key words: Vernal keratoconjunctivitis, New-onset VKC Adult-onset VKC Ocular manifestations of HIV Allergy Immunocompromised.

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