MELAS COME PARADIGMA DELLO STROKE-LIKE

Slides:



Advertisements
Similar presentations
Management of Stroke and Transient Ischaemic Attack Sam Thomson.
Advertisements

Medical Genetics 13 线粒体疾病 mitochondrial diseases.
Fran D. Kendall, M.D. Virtual Medical Practice, LLC Biochemical Genetics, Pediatrics Metabolic, Mitochondrial & Inherited Disorders © Copyright 2011 Fran.
First Department of Internal Medicine, General Hospital of Rhodes,
Diffuse Encephalitis Diagnosed on PET/CT Acquired in a Patient in Status Epilepticus with Negative MRI J Cain 1,2, J Hill 2, C Coutinho 2, S Mathur 2 1.
Inflammatory Cerebral Amyloid Angiopathy
VIRAL ENCEPHALITIS A range of viruses can cause encephalitis but only a minority of patients have a history of recent viral infection. In Europe, the most.
Brain Tumors Maria Rountree. Most common types of brain tumors The most common childhood tumors are: The most common childhood tumors are: 1. Astrocytoma.
Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes (MELAS)
Radiation Injury Can Mimic Tumor Progression Following Proton Radiotherapy for Atypical Teratoid Rhabdoid Tumor in Pediatric Patients M Chang 1, F Perez.
The Brain. Problems with the Brain… Dementia – group of symptoms affecting intellectual and social abilities severely enough to interfere with daily.
Seizure Disorders in Children Maura B. Price MD FRCPC FAAP February 2010
1 Communication Problems of the Elderly Dementia Laryngeal and Vocal Function Hearing and Balance Vision Problems.
Abstract No: D Shaw 1, T Ahmed 2, M Islam 2, G Ishak 1 1 Seattle Children's Hospital, University of Washington; Seattle, WA 2 Dhaka Hospital of.
Sagittal FLAIR images - Stable nonenhancing hyperintensities within the pericallosal white matter and bilateral centrum semiovale, consistent with known.
HERPES SIMPLEX ENCEPHALITIS ENCEPHALITIS M.RASOOLINEJAD, MD DEPARTMENT OF INFECTIOUS DISEASE TEHRAN UNIVERCITY OF MEDICAL SCIENCE.
Transient Global Amnesia – Late middle age – Anterograde and retrograde amnesia – Resolves within hours – Recurrences in 20% of patients – Postulated.
Out-patient Management in Neurology
9 th Medical Genetic Course Center for Biomedical Researh (CEBIOR), Diponegoro University, Semarang, Indonesia In collaboration with Radboud University.
Imaging Spectrum of Herpes Encephalitis In Paediatric Brain Abstract IDNo: 90.
Subarachnoid Hemorrhage. Etiology Spontaneous (primary) subarachnoid hemorrhage usually results from ruptured aneurysms. A congenital intracranial saccular.
Neurobiology of Dementia Majid Barekatain, M.D., Associate Professor of Psychiatry Neuropsychiatrist Isfahan University of Medical Sciences Ordibehesht.
Wernicke’s encephalopaty: the best way to make early diagnosis D.MACHADO* – A.BOCCHIO *– A.M.ROSANO’*- M.OGGERO*- N.MILLOZ° – G.DOVERI°– T.MELONI* *Radiology.
Chewarat Wirojtananugoon, MD. Jiraporn Laothamatas, MD.
AMPK predicted structure C-terminus Thr-172 N-terminus.
Diseases and Disorders of the Nervous System. schizophrenia Characterized by psychotic episodes involving hallucinations & delusions Genetic & environmental.
KEARNS-SAYRE SYNDROME (KSS) By: Emily Tucker. When did Kearns-Sayre Come About?  Thomas P. Kearns and George Pomeroy Sayre (1958)  Clinical triad of.
Neurotoxicity of Immunosuppressive drugs 신장내과 R3 김경엽.
Fran D. Kendall, M.D. Virtual Medical Practice, LLC Biochemical Genetics, Pediatrics Metabolic, Mitochondrial & Inherited Disorders Mitochondrial Disease.
Archana Rao, MD. What is it?? Stroke occurs when there is inadequate blood flow to a part of the brain Or a hemorrhage that occurs into the brain Both.
Epilepsy Dr. Shreedhar Paudel May, Epilepsy… Recurrent, paroxysmal, involuntary clinical events associated with abnormal electrical activity from.
The Malfunctioning Mind: Degenerative Diseases of the Brain
Nervous System Disorders and Homeostatic Imbalances
Copyright © 2002 American Medical Association. All rights reserved.
55 year-old man with acute headache and dizziness Teaching NeuroImages Neurology Resident and Fellow Section David Yen-Ting Chen, MD Ying-Chi Tseng, MD.
mitochondrial myopathies
Cerebrovasc Dis 2014;37: DOI: /
POLG1 mutations should be considered in teenagers and young adults reporting episodic visual symptoms with migraine-like headaches and sudden-onset intractable.
Yard. Doç.Dr. N. Berfu AKBAŞ
Cerebral Folate Deficiency and It's Management
CASES 7-11.
Red flag neurologic symptoms
POLG1 mutations should be considered in teenagers and young adults reporting episodic visual symptoms with migraine-like headaches and sudden-onset intractable.
Morning Report October 26, 2010.
Organic Mental Disorders
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Review of Literature Zebin Xiao Department of.
Autoimmune Encephalitis
Altered mental status in children
Traumatic Brain Injury (TBI)
How I treat and manage strokes in sickle cell disease
Chapter 93 Dementias and Related Disorders
A healthy 46-year-old woman presented with an acute onset of psychiatric disturbance and hyponatremia. A healthy 46-year-old woman presented with an acute.
2/15/2019 Shadab Salehpour.
Figure 1 MRI, pathology, and EEG findings(A) Axial fluid-attenuated inversion recovery (FLAIR) MRI sequences of the brain showing right frontal and parietal.
CLINICAL PROBLEM SOLVING
Neurological complications of diabetes mellitus, anemia, alcoholism, collagenous disorders DM,
Hashimoto’s Encephalitis
Review of diffuse cortical injury on diffusion-weighted imaging in acutely encephalopathic patients with an acronym: “CRUMPLED”  Yasemin Koksel, John.
Cellular Disorders.
Figure 1 Radiologic features of patients with white matter syndromes in association with NMDA receptor antibodies Radiologic features of patients with.
Evaluation and Management of Pediatric Seizures
A 2 year old girl with progressive neurological deficits
A 11-month-old girl with acute irritability and hypotonia
LHON/LHON plus Andrea Gropman, M.D., FAAP, FACMG, FANA
Images from the case of a 31-year-old man with MELAS syndrome, which was documented by a point mutation in the mitochondrial tRNA (Leu). Images from the.
Anti-voltage-gated calcium channel encephalitis.
Patient 1 is a 39-year-old man with baseline blood pressure 122/61 mm Hg who had severe pneumonia with bronchial obstruction. Patient 1 is a 39-year-old.
A 42-year-old woman who presented with altered mental status and lethargy. A 42-year-old woman who presented with altered mental status and lethargy. FLAIR.
Presentation transcript:

MELAS COME PARADIGMA DELLO STROKE-LIKE Costanza Simoncini Università di Pisa

Monogenic diseases and juvenile ischemic stroke       Dichgans 2007 Terni et al, BBA 2015 2

MELAS MITOCHONDRIAL ENCEPHALOMYOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES Acute episodes can present at any age with neurological and/or psychiatric symptoms typically associated with cortical/subcortical MRI changes and EEG abnormalities. Stroke-like: metabolic stroke! Recurrent stroke-like episodes: mostly posterior lesions Mutation A3243G tRNA Leu gene but also other tRNA mutations and POLG

MELAS clinical features   Stroke-like episodes 100% Focal or generalized seizures 85-96% Migraine-like headaches 77-92% Dementia 65-90% Mitochondrial myopathy 87-89% Short stature 55-95% Hypertrophic cardiomyopathy 7-18% PEO 13% Diabetes 21% Hearing loss 27-75% Family history consistent 20-86% Lactic acidosis 94-97% Thambisetty 2002 4

WORKS FROM THE ITALIAN NETWORK

MELAS: stroke-like lesions mitochondrial angiopathy blood-brain barrier permeability toxic effect of lactic acid pH vasogenic edema focal neuronal dysfunction inability to respond to high energy demand seizures

MELAS neuroradiological features right temporo-parietal and thalamic lesions Spectroscopy: lactate peak in the lesion and in the CSF DWI MRI Migrant injuries: spread slowly (weeks - months from the onset of symptoms) from the temporal cortex to the parietal and occipital cortex During the episodes: - Vasodilatation for lactic acidosis (not ischemia!) - Vasogenic edema 8

Selection of take home messages from m.3243 MELAS cases

Medical history: hearing loss MELAS: stroke-like episodes Atipical case 45 years ER: episodes of confusion and headache in last 3 weeks, two generalised seizures followed by coma (GCS 5). family history: negative for neuromuscular or neurodegenerative disorders Medical history: hearing loss Brain MRI showed temporal lobes T2 hyperintensity with diffusion restriction and contrast uptake and bilateral temporal lobes T1 hyperintensity. Proton spectroscopy showed a lactate peak with reduction of N-Acetyl-Aspartate. CSF presented increased proteins, glucose and lactate but not white cells. Increased lactate was also present in serum.

Genetic testing showed the 3243A> G mtDNA mutation in urine 2 gr endovenous carnitine and 600 mgs of coenzyme Q10 AEDs, NO ARGININE!!! Rapid clinical improvement (GCS 13) and regression of the lactic acidosis A one-month later brain MRI showed regression of cerebral edema and marked lactate reduction Genetic testing showed the 3243A> G mtDNA mutation in urine

Case I take home messages Poor knowledge in no mito expert setting (not only stroke, but also encephalitys mimic) Full recovery with carnitene, AEDs and coq, NO ARGININE

Case II Age 20: Migraine, cortical blindness and status epilepticus partial No family history

Age 20: Migraine, cortical blindness and status epilepticus partial right temporo-parietal and thalamic lesions Spectroscopy: lactate peak in the lesion and in the CSF m.15092G>A cyt b p.G116S

enisa

A C D B

Case II take home message Chraniotomy in selected cases

Case III A 41-year-old woman –teacher- complained of subacute afasia, followed by one focal motor seizure Clinical and family history both negative

Case III Four months after.. m.3243 in urine Tp: l-arg, coq10, carnitene, riboflavine and delorazepam, aloperidol, cbz Four months after..

Acute negative symptoms Acute negative symptoms. Loss of interest in ADL, hypersonnia, negative symptoms, such as depressed mood, loss of interest in activities, psychomotor retardation, refuse of food and liquid, bedridden Diagnosis: catatonia Tp: aloperidol, BDZ (lorazepam, delorazepam, diazepam,), promazine Almost 20 days at the hospital!

Case III take home message Catatonia & psichosis An alert for psychiatrists

Case IV 48-yrs Acute aphasia and partial motor seizures Mild eyelid ptosis Previous medical history negative

m.3243 in urine Tp: l-arg, coq10, LEV, cbz One year after…..

Acute visual hallucination ER-> ophtalmologist (sic) -> discharged at home Few days after also confusion……

Larg ev. LEV, CBZ

Case IV take home message Visual hallucination very typical but: WHO KNOWS?? Stroke like episode driven by SEIZURE activity -> potentially treatable??

29

MANAGEMENT There is no specific consensus approach for treating individuals with MELAS syndrome. All patients suspected to be suffering a stroke-like episode due to underlying mitochondrial disease should be discussed or referred to a mitochondrial disease specialist in the acute setting. Monitoring for the development of arrhythmia Gastroparesis and small bowel intestinal pseudo-obstruction

BEYOND NEUROLOGY -cardiopathy -liver imp. -diabetes -lactic acidosis SNC: stroke like episodes and… -seizures & myoclonus -ataxia -cognitive imp. -mov. disorders -optic atrophy -NSHL -psycomotor imp. And hallucinations NEUROMUSCULAR -PEO -Exercise intolerance -Weakness, fatigue, ex.int. -wasting -dysphagia -numbness -paresthesia BEYOND NEUROLOGY -cardiopathy -liver imp. -diabetes -lactic acidosis As a general hint, the apparently unrelated involvement of two or more tissues should suggest the possibility of mitochondrial disease, including the cases where the family history is unremarkable

MANAGEMENT L-Arginine 0.5 g/kg AEDs (no valproic acid) CoQ10 Riboflavin Creatine No antiplatelet therapy of fibrinolisis!

Thank you