scholarly journals Late Onset Atypical Pantothenate-Kinase-Associated Neurodegeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Natalie Diaz
Keyword(s):  
Cognitive Impairment ◽  
Genetic Testing ◽  
Late Onset ◽  
Genetic Disorder ◽  
Iron Accumulation ◽  
Pantothenate Kinase ◽  
Radiographic Findings ◽  
Current Time ◽  
Initial Symptoms ◽  
History Of

Introduction. Pantothenate-kinase-associated neurodegeneration (PKAN) is a rare genetic disease and a form of neurodegeneration with brain iron accumulation (NBIA). It most commonly begins in the first two decades of life but should be considered in the differential diagnosis of patients at any age with an atypical progressive extrapyramidal disorder and cognitive impairment. Few late-adult cases have been reported.Case Report. A 50-year-old woman presented with a history of progressive dysarthria and dysphagia secondary to orolingual dystonia. Initial work-up was normal. There was no family history. Her initial symptoms were followed by the onset of blepharospasm, cervical dystonia, Parkinsonism, and cognitive impairment. Follow-up MRI four years after presentation revealed the diagnostic “eye-of-the-tiger” sign. Genetic testing confirmed a homozygous missense mutation consistent with the diagnosis of PKAN.Conclusion. Although PKAN is a rare genetic disorder most commonly seen in childhood, it should be considered in adult patients with a history of progressive focal dystonia or atypical Parkinsonism. As the radiographic findings are quite characteristic, genetic testing should be performed if the MRI shows evidence of iron accumulation. Optimal treatment strategies are not known, and at the current time therapies should be directed at the specific manifestations of the disease.

Microbial clues lead to a diagnosis of cystic fibrosis in late adulthood

2020 ◽  
Vol 13 (4) ◽  
pp. e233470
Author(s):  
Colm Kerr ◽  
David Morrissy ◽  
Mary Horgan ◽  
Barry J Plant
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Genetic Disorder ◽  
Good Effect ◽  
Transmembrane Conductance Regulator ◽  
Old Irish ◽  
Common Life ◽  
Sweat Testing ◽  
History Of ◽  
Tract Infections

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive genetic disorder among Caucasian populations. The majority of CF cases are diagnosed in childhood; however, increasing numbers of adults are being diagnosed with the condition. We present the case of a 65-year-old Irish woman presenting with a chronic cough and a history of recurrent respiratory tract infections. Staphylococcus aureus, Scedosporium apiospermum and Stenotrophomonas maltophilia were grown from bronchoalveolar lavage raising suspicion for CF. Sweat testing was negative; however, genetic testing revealed the presence of ∆F508 and R117H CF mutations, the latter mutation conferring a milder form of CF. The patient commenced treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator medication ivacaftor to good effect. Novel CFTR potentiators and modulators have significant potential to benefit morbidity and mortality in this group. In this case, the microbiological results were key in pursuing genetic testing and diagnosing CF.

Valproate-induced fatal acute hyperammonaemia-related encephalopathy in late-onset ornithine transcarbamylase deficiency

2021 ◽  
Vol 14 (5) ◽  
pp. e241429
Author(s):  
Daniel Kazmierski ◽  
Nishant Sharma ◽  
Kelly O'Leary ◽  
Pius Ochieng
Keyword(s):  
Cerebral Oedema ◽  
Urea Cycle ◽  
Late Onset ◽  
Genetic Disorder ◽  
Management Strategies ◽  
Ornithine Transcarbamylase ◽  
Ornithine Transcarbamylase Deficiency ◽  
History Of ◽  
Otc Deficiency ◽  
Psychiatric Conditions

Ornithine transcarbamylase (OTC) deficiency is a genetic disorder of the urea cycle characterised by deficiency in the enzyme OTC, resulting in an accumulation of ammonia. Valproic acid (VPA), a commonly used medication in the treatment of neurologic and psychiatric conditions, has been known to cause episodes of acute hyperammonaemia in patients with OTC deficiency. We present the case of a 29-year-old man with a long history of non-specific psychiatric disorders, who suffered from a hyperammonaemic crisis following the administration of VPA, leading to the diagnosis of OTC deficiency. The patient’s hospital course was complicated by progressive cerebral oedema, which resulted in worsening encephalopathy, seizures and death. We discuss the pathophysiology of hyperammonaemia in OTC deficiency, and various management strategies, including lactulose, levocarnitine, scavenger therapy and haemodialysis.

062 Cadasil presenting with focal and generalised epilepsy due to a novel NOTCH3 mutation

2018 ◽  
Vol 89 (6) ◽  
pp. A25.3-A26 ◽  
Author(s):  
Benson S Chen ◽  
James C Cleland ◽  
Richard I King ◽  
Neil E Anderson
Keyword(s):  
Cognitive Impairment ◽  
Genetic Testing ◽  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Family Members ◽  
Clinical Manifestations ◽  
Prior History ◽  
Notch3 Mutation ◽  
History Of ◽  
Strong Segregation

IntroductionCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease caused by mutations of the NOTCH3 gene. Clinical manifestations include migraine, recurrent ischaemic strokes, and cognitive decline. Seizures are an uncommon early symptom and usually occur after the onset of stroke. We report a CADASIL family with epilepsy as an early clinical symptom due to a novel NOTCH3 mutation.MethodsThe clinical histories of three family members from two generations are reported, alongside para-clinical details including results of magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic testing.ResultsThe proband developed focal and generalised seizures at age 51. She had a preceding history of cognitive impairment and migraines. The proband’s son developed focal seizures at age 25 involving his left arm and then generalised seizures. He experienced intermittent headaches, without history of stroke or cognitive impairment. His sister (the proband’s daughter) had epilepsy from age 12, characterised by blank spells and generalised seizures. Cognitive decline was noted from age 38, without history of stroke. There was no family history of epilepsy in those without CADASIL. MRI in all three family members showed multifocal T2 FLAIR hyperintensities within the supratentorial white matter, particularly the temporal lobes. EEG was abnormal only in the proband’s son, with paroxysmal bursts of poorly organised 3–4 Hz spike-wave activity. Genetic testing in all three family members found a novel NOTCH3 mutation, c.1337G>A p.(Cys446Tyr).ConclusionWe have identified a novel NOTCH3 mutation in a kindred with epilepsy as an early manifestation of CADASIL without prior history of strokes. The association with epilepsy is unlikely to be coincidental given the strong segregation of epilepsy and CADASIL in this kindred and the clear focal seizure semiology noted in all family members. Whether this mutation represents a distinct new phenotype requires further investigation.

Late-Life Depressive Disorder in the Community

1995 ◽  
Vol 166 (3) ◽  
pp. 311-315 ◽  
Author(s):  
Rob Van Ojen ◽  
Chris Hooijer ◽  
Dick Bezemer ◽  
Cees Jonker ◽  
Jaap Lindeboom ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Late Onset ◽  
First Episode ◽  
Psychiatric History ◽  
Elderly Individuals ◽  
Stratified Sample ◽  
History Of ◽  
The Relationship ◽  
State Examination ◽  
Young Old

BackgroundIn previous studies cognitive impairment in depressed elderly in-patients tends to be associated with a late onset of depression. This study tests the hypothesis that cognitive impairment is associated with depression only in elderly individuals with no history of psychiatric illness.MethodWe investigated an age-stratified sample of 4051 elderly people living in the community, aged between 65 and 84 (AMSTEL). The relationship between depression (GMS-AGECAT diagnosis) and scores on the Mini Mental State Examination was studied in subjects with and without a reported psychiatric history (CAMDEX questionnaire).ResultsLow MMSE scores (MMSE ≤ 25) were only associated with depression in subjects with no psychiatric history (young/old: OR = 2.75, 95% CI = 1.83, 4.19; old/old: OR = 2.21, 95% CI = 1.61, 3.03).ConclusionsWe concluded that the combination of cognitive impairment and first-episode depression in elderly individuals may indicate cerebral deterioration. Depression as such may not be associated with cognitive impairment.

Enhanced Vocational Rehabilitation: A Pilot for Veterans With Cognitive Impairment and a History of Mild TBI

2012 ◽  
Author(s):  
Maureen K. O'Connor ◽  
Lisa Mueller ◽  
Alicia Semiatin ◽  
Charles E. Drebing ◽  
Shihwe Wang
Keyword(s):  
Cognitive Impairment ◽  
Vocational Rehabilitation ◽  
Mild Tbi ◽  
History Of

An Obscure Colon Dilatation and its Underlying Cause: Case Report and Literature Review

2020 ◽  
pp. 1-5
Author(s):  
Anton Stift ◽  
Kerstin Wimmer ◽  
Felix Harpain ◽  
Katharina Wöran ◽  
Thomas Mang ◽  
...  
Keyword(s):  
Case Report ◽  
Sigmoid Colon ◽  
Immunohistochemical Staining ◽  
Late Onset ◽  
Hirschsprung Disease ◽  
Endoscopic Examination ◽  
Case Presentation ◽  
Idiopathic Megacolon ◽  
History Of ◽  
Cells Of Cajal

Introduction: Congenital as well as acquired diseases may be responsible for the development of a megacolon. In adult patients, Clostridium difficile associated infection as well as late-onset of Morbus Hirschsprung disease are known to cause a megacolon. In addition, malignant as well as benign colorectal strictures may lead to intestinal dilatation. In case of an idiopathic megacolon, the underlying cause remains unclear. Case Presentation: We describe the case of a 44-year-old male patient suffering from a long history of chronic constipation. He presented himself with an obscurely dilated large intestine with bowel loops up to 17 centimeters in diameter. Radiological as well as endoscopic examination gave evidence of a spastic process in the sigmoid colon. The patient was treated with a subtotal colectomy and the intraoperative findings revealed a stenotic stricture in the sigmoid colon. Since the histological examination did not find a conclusive reason for the functional stenosis, an immunohistochemical staining was advised. This showed a decrease in interstitial cells of Cajal (ICC) in the stenotic part of the sigmoid colon. Discussion: This case report describes a patient with an idiopathic megacolon, where the underlying cause remained unclear until an immunohistochemical staining of the stenotic colon showed a substantial decrease of ICCs. Various pathologies leading to a megacolon are reviewed and discussed.

Depression in Dementia or Dementia in Depression? Systematic Review of Studies and Hypotheses

2020 ◽  
Vol 17 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Agnieszka Brzezińska ◽  
Julius Bourke ◽  
Rayito Rivera-Hernández ◽  
Magda Tsolaki ◽  
Joanna Woźniak ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Randomised Controlled Trials ◽  
Late Onset ◽  
Alternative Hypothesis ◽  
Controlled Trials ◽  
Major Depressive ◽  
Future Studies ◽  
Individual Vulnerability ◽  
Current Review ◽  
Randomised Controlled

The majority of research works to date suggest that Major Depressive Disorder (MDD) is a risk factor for dementia and may predispose to cognitive decline in both early and late onset variants. The presence of depression may not, however, reflect the cause, rather, an effect: it may be a response to cognitive impairment or alters the threshold at which cognitive impairment might manifest or be detected. An alternative hypothesis is that depression may be part of a prodrome to Alzheimer’s Disease (AD), suggesting a neurobiological association rather than one of psychological response alone. Genetic polymorphisms may explain some of the variances in shared phenomenology between the diagnoses, the instance, when the conditions arise comorbidly, the order in which they are detected that may depend on individual cognitive and physical reserves, as well as the medical history and individual vulnerability. This hypothesis is biologically sound but has not been systematically investigated to date. The current review highlights how genetic variations are involved in the development of both AD and MDD, and the risk conferred by these variations on the expression of these two disorders comorbidly is an important consideration for future studies of pathoaetiological mechanisms and in the stratification of study samples for randomised controlled trials.

Voltage-gated potassium channel limbic encephalitis presenting as functional cognitive impairment

2020 ◽  
Vol 13 (12) ◽  
pp. e233179
Author(s):  
Eric Garrels ◽  
Fawziya Huq ◽  
Gavin McKay
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Psychiatric Symptoms ◽  
Differential Diagnoses ◽  
Visual Hallucinations ◽  
Voltage Gated ◽  
History Of ◽  
Impaired Cognition

Limbic encephalitis is often reported to present as seizures and impaired cognition with little focus on psychiatric presentations. In this case report, we present a 49-year-old man who initially presented to the Psychiatric Liaison Service with a several month history of confusion with the additional emergence of visual hallucinations and delusions. Due to the inconsistent nature of the symptoms in the context of a major financial stressor, a provisional functional cognitive impairment diagnosis was made. Investigations later revealed a positive titre of voltage-gated potassium channel (VGKC) antibodies, subtype leucine-rich glioma inactivated 1 accounting for his symptoms which dramatically resolved with steroids and immunoglobulins. This case highlighted the need for maintaining broad differential diagnoses in a patient presenting with unusual psychiatric symptoms.

scholarly journals National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer

2017 ◽  
Vol 35 (34) ◽  
pp. 3800-3806 ◽  
Author(s):  
Christopher P. Childers ◽  
Kimberly K. Childers ◽  
Melinda Maggard-Gibbons ◽  
James Macinko
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Unmet Need ◽  
Cancer Control ◽  
The United States ◽  
Eligibility Criteria ◽  
Cross Sectional ◽  
Age Of Diagnosis ◽  
History Of ◽  
Interview Survey

Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.

scholarly journals R1352Q CACNA1A Variant in a Patient with Sporadic Hemiplegic Migraine, Ataxia, Seizures and Cerebral Oedema: A Case Report

2021 ◽  
pp. 123-130
Author(s):  
Anker Stubberud ◽  
Emer O’Connor ◽  
Erling Tronvik ◽  
Henry Houlden ◽  
Manjit Matharu
Keyword(s):  
Mental Retardation ◽  
Case Report ◽  
Genetic Testing ◽  
Head Trauma ◽  
Cerebral Oedema ◽  
De Novo ◽  
Minor Head Trauma ◽  
Hemiplegic Migraine ◽  
Wide Range ◽  
History Of

Mutations in the <i>CACNA1A</i> gene show a wide range of neurological phenotypes including hemiplegic migraine, ataxia, mental retardation and epilepsy. In some cases, hemiplegic migraine attacks can be triggered by minor head trauma and culminate in encephalopathy and cerebral oedema. A 37-year-old male without a family history of complex migraine experienced hemiplegic migraine attacks from childhood. The attacks were usually triggered by minor head trauma, and on several occasions complicated with encephalopathy and cerebral oedema. Genetic testing of the proband and unaffected parents revealed a de novo heterozygous nucleotide missense mutation in exon 25 of the <i>CACNA1A</i> gene (c.4055G&#x3e;A, p.R1352Q). The R1352Q <i>CACNA1A</i> variant shares the phenotype with other described <i>CACNA1A</i> mutations and highlights the interesting association of trauma as a precipitant for hemiplegic migraine. Subjects with early-onset sporadic hemiplegic migraine triggered by minor head injury or associated with seizures, ataxia or episodes of encephalopathy should be screened for mutations. These patients should also be advised to avoid activities that may result in head trauma, and anticonvulsants should be considered as prophylactic migraine therapy.

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