scholarly journals Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment

2018 ◽  
Vol 50 (01) ◽  
pp. 002-014 ◽  
Author(s):  
Heiko Brennenstuhl ◽  
Sabine Jung-Klawitter ◽  
Birgit Assmann ◽  
Thomas Opladen
Keyword(s):  
Neurological Disorders ◽  
Clinical Symptoms ◽  
Quantitative Detection ◽  
Monoamine Neurotransmitters ◽  
Inherited Disorders ◽  
Delay In Diagnosis ◽  
Clinical Onset ◽  
Cofactor Biosynthesis ◽  
Neurotransmitter Precursors ◽  
Peripheral Markers

AbstractNeurotransmitter deficiencies are rare neurological disorders with clinical onset during childhood. The disorders are caused by genetic defects in the enzymes involved in synthesis, degradation, or transport of neurotransmitters or by defects in the cofactor biosynthesis such as tetrahydrobiopterin (BH4). With the newly described DNAJC12 deficiency, a chaperon-associated neurotransmitter disorder, the pathophysiological spectrum has been broadened. All deficiencies result in a lack of monoamine neurotransmitters, especially dopamine and its products, with a subset leading to decreased levels of serotonin. Symptoms can occur already in the neonatal period. Classical signs are hypotonia, movement disorders, autonomous dysregulations, and impaired development. Diagnosis depends on quantitative detection of neurotransmitters in cerebrospinal fluid, since peripheral markers in blood or urine are less reliable. Treatment is based on supplementation of the missing neurotransmitter precursors or restoring deficient cofactors for endogenous enzymatic synthesis. In recent years, knowledge about this orphan group of diseases increased substantially among clinicians. However, the difficult task of integrating clinical symptoms and laboratory values still leads to a critical delay in diagnosis and therapy for patients. This review aims at enhancing the understanding of neurotransmitter disorders and should help practicing clinicians to choose useful diagnostic steps on the way to a valid diagnosis.

scholarly journals Analysis of Catecholamines and Pterins in Inborn Errors of Monoamine Neurotransmitter Metabolism—From Past to Future

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 867 ◽  
Author(s):  
Sabine Jung-Klawitter ◽  
Oya Kuseyri Hübschmann
Keyword(s):  
Quantitative Detection ◽  
Acid Decarboxylase ◽  
Monoamine Neurotransmitter ◽  
Inborn Errors ◽  
Amino Acid Decarboxylase ◽  
Different Types ◽  
Genes Encoding ◽  
Cofactor Biosynthesis ◽  
Analytical Tools ◽  
Neurotransmitter Precursors

Inborn errors of monoamine neurotransmitter biosynthesis and degradation belong to the rare inborn errors of metabolism. They are caused by monogenic variants in the genes encoding the proteins involved in (1) neurotransmitter biosynthesis (like tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC)), (2) in tetrahydrobiopterin (BH4) cofactor biosynthesis (GTP cyclohydrolase 1 (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), sepiapterin reductase (SPR)) and recycling (pterin-4a-carbinolamine dehydratase (PCD), dihydropteridine reductase (DHPR)), or (3) in co-chaperones (DNAJC12). Clinically, they present early during childhood with a lack of monoamine neurotransmitters, especially dopamine and its products norepinephrine and epinephrine. Classical symptoms include autonomous dysregulations, hypotonia, movement disorders, and developmental delay. Therapy is predominantly based on supplementation of missing cofactors or neurotransmitter precursors. However, diagnosis is difficult and is predominantly based on quantitative detection of neurotransmitters, cofactors, and precursors in cerebrospinal fluid (CSF), urine, and blood. This review aims at summarizing the diverse analytical tools routinely used for diagnosis to determine quantitatively the amounts of neurotransmitters and cofactors in the different types of samples used to identify patients suffering from these rare diseases.

scholarly journals A broad spectrum of posterior reversible encephalopathy syndrome - a case series with clinical and paraclinical characterisation, and histopathological findings

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatme Seval Ismail ◽  
Johannes van de Nes ◽  
Ilka Kleffner
Keyword(s):  
Posterior Reversible Encephalopathy Syndrome ◽  
Clinical Symptoms ◽  
Brain Mri ◽  
Case Series ◽  
Epileptic Seizures ◽  
Retrospective Case ◽  
Posterior Reversible Encephalopathy ◽  
Histopathological Findings ◽  
Delay In Diagnosis ◽  
Reversible Encephalopathy

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is clinical-neuroradiologically defined and potentially reversible, so there are limited data about histopathological findings. We aimed to describe the clinical and paraclinical features of patients with PRES with regard to its reversibility. Methods This retrospective case series encompasses 15 PRES cases out of 1300 evaluated patients from a single German center between January 1, 2010, and June 15, 2020. PRES was established according to the diagnostic criteria as proposed by the Berlin PRES Study 2012. One of the cases studied was subject to brain autopsy. Results From the 15 patients studied (median age 53 years, range 17–73; 11 female), 67 % presented with epileptic seizures, 40 % suffered from encephalopathy with reduced consciousness and 53 % developed delirium, while 47 % had headache and visual disturbances. Subcortical brain MRI abnormalities related to PRES were observed in all patients. One patient developed spinal ischemia and another Guillain-Barré syndrome in addition to PRES. Hypertensive blood pressure was the main underlying/trigger condition in all patients. Clinical symptoms and MRI changes were not reversible in 42 %, even progressive in 3 out of these 5 patients. Median time from symptom onset to diagnosis in these non-reversible cases was 7 days (range 0–13), while the median delay in diagnosis in the reversible group was 1 day (range 0–3). Cerebellar/brain stem involvement and status epilepticus were more frequently in patients with non-reversible disease course. Mortality due to PRES occurred in 13 % of these patients. Neuropathological examination of the brain of a 57-year-old female patient revealed major leukencephalopathic changes, fibrinoid necrosis of endothelial cells and fresh petechial hemorrhages in accordance with PRES. Conclusions Our case series demonstrates that PRES was not reversible in 42 % of the studied patients. Delay in diagnosis seems to contribute to limited reversibility and poor outcome.

Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India

2017 ◽  
Vol 71 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Kirti Gupta ◽  
Amit Rawat ◽  
Parimal Agrawal ◽  
Ankur Jindal ◽  
Ritambhra Nada ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Bacterial Infections ◽  
Clinical Symptoms ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Case Reports ◽  
Infectious Complications ◽  
North India ◽  
Inherited Disorders ◽  
Primary Immunodeficiency Disorders

BackgroundPrimary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports.ObjectiveTo analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade.MethodsStudy includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders.ResultsA varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature.ConclusionsThe present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.

scholarly journals Outcome of acute Myeloid Leukemia in Adults Patients Treated According to Morocco National AML-MA-2011 Protocol in Casablanca, Morocco

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5173-5173
Author(s):  
Romaric Massi ◽  
Mouna Lamchahab ◽  
Hanaa Bencharef ◽  
Bienvenu Houssou ◽  
Nisrine Khoubila ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Complete Remission ◽  
Supportive Care ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
International Standards ◽  
Banding Technique ◽  
Persistent Fever ◽  
Delay In Diagnosis

Abstract Introduction Treatment of AML in developing countries is a very great challenge. In Morocco, the major causes of therapy failure are delay in diagnosis, early (prior to start of therapy) and induction deaths, induction failures and abandonment of therapy. In 2011, the national AML-MA-2011 protocol was initiated to treat AML patients according to international standards and was focused on the improvement of supportive care with particular the prevention and management of infection, transfusion support, the patient, family and nurses education on hygien. The objective of this new protocol was to obtained more than 70% of complete remission, deaths in inductions less than 10%, and EFS at 4years at 40%. The aim of this study is to evaluate the results in adults AML patients treated with AML MA 2011 protocol in Casablanca Hematology Departement. Patients and Methods : Were reviewed the data ofpatients (aged 18-60yrs) treated according to AML-MA-2011 protocol from 1st january 2011 to 31th december 2015. Patients with APL or secondary AML were excluded. AML was diagnosed by studying peripheral blood smears, bone marrow aspiration, and biopsy slides stained with May-Grünwald Giemsa and myeloperoxidase. Immunophenotypic and cytogenetic studies were performed at diagnosis on bone marrow samples. AML was defined as the presence of more than 20% of myeloblasts in the bone marrow. Subtype of AML was recorded according to French-American-British (FAB) classification. Karyotype was performed on marrow sample, R banding technique was used. WHO 2008 prognostic classification was adopted. Patients with hyperleukocytosis (WBC≥ 50G/L) received as a pre-phase 4 days of hydroxyurea to 50mg/kg/day. The two courses of induction associated Cytarabine (100mg/m² q 12h (day 1-10)), Daunorubicin (50 mg/m² (day 2, 4, 6) for the first course, on days 1, 3, 5 for the second course) and etoposide (100mg/m² only at second course of induction). The consolidation included Cytarabine (3g/m² q 12h (day1-3) for first and second course and 1 g/m² (day1-3) on third course) plus Daunorubicin (30mg/m² (day 3-4 and day 1-3) at the first and third consolidation. L-Asparaginase 6000UI/m² on day 4 was give at second consolidation. Patients received CNS prophylaxis. Platelet support was provided in the case of bleeding, or whenever the platelet count was less than 10 × 109/L. For infections, Ceftazidime was the first line of antibiotic used. Amikacin was added for persistent fever beyomd 48-h or clinical deterioration. Imipenem was used for persistent fever. Additional antibiotic or antifungal or antiviral was dictated by clinical and biological findings. Complete remission (CR) was defined as the absence of abnormal clinical symptoms and having less than 5% of myeloblasts in the bone marrow, absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 × 109/L; platelet count >75 × 109/L; independence of red cell transfusions. The analysis of data was done by SPSS 18.0 Résultats : 559 adults patients were diagnosed for AML,323 was treated by AML-MA-2011 protocol from 2011-2015. The median age was 38 years (18-60), the sex ratio M/F was 1.10 ; the median hemoglobin (g/dl) was 7.15 (2.6-16.3) ; the median platelet (G/L) was 38.5 (1-620) ; the median leukocyte (G/L) was 17.97 (0.85-377). For cytology, according to FAB the dominants types was M1 : 98 (30.34%), M2 : 97 (30.03%), M4 : 51(15.78%). 249 (77.08%) patients had immunophenotyping. According to karyotype, 46 (14.24%) had good prognosis ; 216 (66.87%) was in intermediate group, 61 (18.88%) had adverse prognosis. Complete remission after two inductions was obtained with 197(60.99%) patients, inductions failure was noticed on 49(15.17%) patients, 98(30.34%) patients died during inductions cycles ; 152(47.05%) achieved the second consolidation cycles, 66 (33.50%) patients whose were in complete remission relapse. The OS at 3-years was estimated at 48.4%. The analysis of therapeutics results is summarized in the table. Conclusion : The therapeutics results of AML-MA-2011 protocol in the treatement of adults AML patients are satisfactory but could be improved with reduction of infection toxic deaths and improvement of supportive care therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical profile of patients with Seronegative celiac disease

2022 ◽  
Author(s):  
Elham Rahmanipour ◽  
fahimeh attarian ◽  
Mohammad Ghorbani ◽  
Bijan Shahbazkhani ◽  
Vahid Ghavami ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Poor Prognosis ◽  
Clinical Symptoms ◽  
Challenge Test ◽  
Iga Deficiency ◽  
Clinical Profile ◽  
Positive Serology ◽  
Mucosal Atrophy ◽  
Delay In Diagnosis ◽  
The Mean

Abstract Background Celiac disease (1) mostly diagnosed base on positive serology and duodenal mucosal atrophy, but some patients have negative serology and their diagnosis have some limitation, it delay in diagnosis likely accompanied a poor prognosis and high risk of developing complications of CD. The aim of this study was determent clinical profile of patients with Seronegative CD (SNCD). Methods in this retrospective study, 1115+8 patients, that evaluated for CD with mucosal atrophy included between 2010 to2020. All patients with IgA deficiency other IgG based serology for diagnosis of celiac was done and if these antibodies were negative consider as possible SNCD. If they had positive DQ2-DQ8, and clinical symptoms or had positive challenge test after12 months of GFD were considered as SNCD. Results of total 1115 patients 27 (2.4%) had seronegative mucosal atrophy of duodenum and diagnosed as a SNCD (96.2% marsh3), the mean age and BMI in SNCD patients were significantly higher than other CD patients (p<0.05). Conclusion The prevalence of SNCD was 2.4% that likely related to over weighting, so clinicians should be considered high possible of seronegative CD in patients with over weighting and mucosal atrophy of duodenum.

scholarly journals Clinical and laboratory features of 48 feline hyperthyroidism cases in Japan

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Shinichi Namba ◽  
Nami Matsubara ◽  
Mayuko Ishikawa ◽  
Yurie Arase ◽  
Akiko Doi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Neurological Disorders ◽  
Hind Limb ◽  
Clinical Symptoms ◽  
Endocrine Disorder ◽  
Significant Difference ◽  
Laboratory Features ◽  
Complete Blood Counts ◽  
Hind Limb Paralysis

Feline hyperthyroidism (HT) is a common endocrine disorder worldwide, but clinical and laboratory features might vary geographically. The aim of this retrospective study was to evaluate feline HT in Japan, and compare results to those of previous study for feline HT. We evaluated 48 feline HT cases clinical and laboratory features. Surprisingly, the youngest patient was 32 months of age (2 year 9 months). There was no significant difference among the study subjects in sex, but frequency of spayed/castrated cats was high (85.4%). Median age was 186 months (32-272 months). 91.3% (n=42) of subjects were over 10 years of age, and 8.7% (n=4) were under 10 years of age. Clinical symptoms included vomiting, 56.3% (n=27); diarrhea, 2.1% (n=1); hyperactivity, 12.5% (n=6); emaciation, 41.7% (n=20); polyuria and polydipsia, 22.9% (n=11); chronic weight loss, 60.4% (n=29); and palpated enlarged thyroid, 2.1% (n=1). Concurrent findings included chronic kidney disease, 20.8% (n=10); congestive heart failure, 20.8% (n=10); tachycardia (over 240 beats/min), 18.8% (n=9); gallop rhythm, 31.3% (n=15); neurological disorders such as hind-limb paralysis, 14.6% (n=7); cystitis, 8.7% (n=4); gingivitis, 4.2% (n=2); diabetes mellitus, 4.2% (n=2); and arterial thromboembolism, 6.3% (n=3). In addition, laboratory features (complete blood counts and biochemistry) differed from those of previous reports in certain respects. Our results show that it might be important for practitioners to comprehend epidemiologic differences regarding feline HT worldwide.

Pseudoaneurysm of the popliteal artery due to osteochondroma of the distal femur

VASA ◽  
2010 ◽  
Vol 39 (3) ◽  
pp. 274-277 ◽  
Author(s):  
Sadeghi-Azandaryani ◽  
Mendl ◽  
Rademacher ◽  
Hoffmann ◽  
Steckmeier ◽  
...  
Keyword(s):  
Popliteal Artery ◽  
Neurological Disorders ◽  
Distal Femur ◽  
Bone Tumour ◽  
Vascular Disorders ◽  
Delay In Diagnosis ◽  
Pseudoaneurysm Formation ◽  
Benign Bone Tumour ◽  
Life Threatening ◽  
Hospital Stays

Osteochondroma is the most common type of benign bone tumour, and is most often found in the knee region. The lesion is usually clinically silent although it may cause different complications such as fractures of the tumour, bone deformities, neurological disorders, malignant transformation and in rare cases vascular disorders. Vascular disorders include stenosis, occlusions, thrombosis, arteriovenous fistula and in rare cases pseudoaneurysm formation. A delay in diagnosis especially of pseudoaneurysm formation may result in life-threatening situations, extensive operations and lengthy hospital stays. We report the case of a 22-year-old woman with an osteochondroma of the distal femur which caused pseudoaneurysm of the popliteal artery.

Magnetic resonance evidence of cortical onset of multiple sclerosis

2009 ◽  
Vol 15 (8) ◽  
pp. 933-941 ◽  
Author(s):  
M Calabrese ◽  
P Gallo
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Diagnostic Criteria ◽  
Clinical Symptoms ◽  
Final Diagnosis ◽  
Pathological Process ◽  
Clinical Onset ◽  
Normal Appearing White Matter ◽  
Central Nervous System Dysfunction ◽  
Magnetic Resonance Imaging Mri

Background Despite clinical symptoms and signs of central nervous system dysfunction, conventional magnetic resonance imaging (MRI) of the brain and spinal cord may appear normal in multiple sclerosis (MS) at clinical onset. Objective To demonstrate cortical pathology, namely the presence of cortical lesions (CLs) in patients with symptoms/signs suggestive of MS but having normal appearing white matter (WM) on MRI. Methods CLs were disclosed by double inversion recovery (DIR) MRI sequence. The final diagnosis of MS was achieved by the demonstration of the dissemination in space and time of WM lesions, and the absence of a better explanation of symptoms/signs, according to the established international diagnostic criteria. Results We describe four patients with MS, in which CLs were observed by DIR months/years before the MRI evidence of inflammatory lesions in the WM. Interpretation We suggest that, at least in some patients with MS, the pathological process underlying MS starts in the cortex. DIR sequence should be included in the MRI examination of suspected patients with MS with normal conventional MRI sequences at clinical onset. CLs should be evaluated for their inclusion in the MRI diagnostic criteria for MS.

Prion-related peripheral neuropathy in sporadic Creutzfeldt-Jakob disease

2018 ◽  
Vol 90 (4) ◽  
pp. 424-427 ◽  
Author(s):  
Simone Baiardi ◽  
Veronica Redaelli ◽  
Paolo Ripellino ◽  
Marcello Rossi ◽  
Alessia Franceschini ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Western Blotting ◽  
Clinical Symptoms ◽  
Nerve Biopsy ◽  
Plaque Type ◽  
Clinical Onset ◽  
Phenotypic Spectrum ◽  
Neurophysiological Data ◽  
Jakob Disease ◽  
Strain Dependent

ObjectiveTo assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD).MethodsWe examined medical records of 117 sCJDVV2 (ataxic type), 65 sCJDMV2K (kuru-plaque type) and 121 sCJDMM(V)1 (myoclonic type) subjects for clinical symptoms, objective signs and neurophysiological data. We reviewed two diagnostic nerve biopsies and looked for abnormal prion protein (PrPSc) by western blotting and real-time quaking-induced conversion (RT-QuIC) in postmortem PNS samples from 14 subjects.ResultsSeventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms or signs suggestive of PNS involvement occurring at onset in 18 cases (17 VV2-MV2K, 9.3%; and 1 MM(V)1, 0.8%) and isolated in 6. Nerve biopsy showed a mixed predominantly axonal and demyelinating neuropathy in two sCJDMV2K. Electromyography showed signs of neuropathy in half of the examined VV2-MV2K patients. Prion RT-QuIC was positive in all CJD PNS samples, whereas western blotting detected PrPSc in the sciatic nerve in one VV2 and one MV2K.ConclusionsPeripheral neuropathy, likely related to PrPSc deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2 and may mark the clinical onset. The significantly lower prevalence of PNS involvement in typical sCJDMM(V)1 suggests that the PNS tropism of sCJD prions is strain dependent.

Gangliocytic Paraganglioma: a Rare Cause of Gastrointestinal Bleeding

2015 ◽  
Vol 24 (1) ◽  
pp. 109-112 ◽  
Author(s):  
Alina Boeriu ◽  
Daniela Dobru ◽  
Rareș Georgescu ◽  
Simona Mocan ◽  
Cristian Boeriu
Keyword(s):  
Gastrointestinal Bleeding ◽  
Clinical Symptoms ◽  
Disease Recurrence ◽  
Benign Tumors ◽  
Gangliocytic Paraganglioma ◽  
Delay In Diagnosis ◽  
Different Types ◽  
Duodenal Neuroendocrine Tumors ◽  
Upper Gastrointestinal ◽  
Local Tumor Growth

Duodenal neuroendocrine tumors (NETs) are rare tumors, consisting of five different types of tumors. In many cases, they may be asymptomatic, leading to delay in diagnosis. Clinical symptoms are related to local tumor growth and mucosal ulceration. We report a 38-year old man with duodenal gangliocytic paraganglioma causing overt upper gastrointestinal bleeding and anemia. We describe specific clinical and histopathological features of the tumor, and review the diagnostic and therapeutic strategy. Gangliocytic paragangliomas are regarded as benign tumors. However, the disease recurrence and the malignant potential of the tumor have also been reported.

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