Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.

Genetic and Mitochondrial Metabolic Analyses of an Atypical Form of Leigh Syndrome

In this study, we aimed to establish the mitochondrial etiology of the proband’s progressive neurodegenerative disease suggestive of an atypical Leigh syndrome, by determining the proband’s pathogenic variants. Brain MRI showed a constellation of multifocal temporally disparate lesions in the cerebral deep gray nuclei, brainstem, cerebellum, spinal cord along with rhombencephalic atrophy, and optic nerve atrophy. Single voxel 1H MRS performed concurrently over the left cerebral deep gray nuclei showed a small lactate peak, increased glutamate and citrate elevation, elevating suspicion of a mitochondrial etiology. Whole exome sequencing revealed three heterozygous nuclear variants mapping in three distinct genes known to cause Leigh syndrome. Our mitochondrial bioenergetic investigations revealed an impaired mitochondrial energy metabolism. The proband’s overall ATP deficit is further intensified by an ineffective metabolic reprogramming between oxidative phosphorylation and glycolysis. The deficient metabolic adaptability and global energy deficit correlate with the proband’s neurological symptoms congruent with an atypical Leigh syndrome. In conclusion, our study provides much needed insights to support the development of molecular diagnostic and therapeutic strategies for atypical Leigh syndrome.

SARS-CoV-2 precipitated Kasabach-Merritt syndrome in a child with angioma infantile and acute lymphoblastic leukemia: Case Report

Background: We describe an 8-month-old boy with leukemia and SARS-CoV-2 infection who developed Kasabach-Merritt phenomenon. He had a positive SARS-COV-2 RT-PCR sample. Hematologic tests showed coagulopathy and intestinal involvement. She was managed in emergency receiving transfusion support and in hospitalization with social isolation measures, she started propanolol and corticotherapy as initial treatment of infantile angiomas. She presented with symptoms of intestinal obstruction and underwent surgery and evidence of hemorrhagic infarction with foci of intestinal ischemic necrosis, ending in ileostomy. We tried to understand a pathophysiological explanation of the dermatologic and gastrointestinal tract involvement by the virus and the atypical form of COVID-19. Given the emerging evidence of endothelial and vascular involvement in COVID-19, the development of tests to detect vascular lesions may be critical to guide the use of new therapeutic strategies.

MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN ASSOCIATED WITH COVID-19: RESULTS OF A MULTICENTER STUDY

Coronavirus disease 2019 (COVID-19) in children in most cases is asymptomatic or mild, and its most severe late complication is multisystem inflammatory syndrome in children (MIS-C). The aim of the study is to find clinical, laboratory and instrumental characteristics, description of therapeutic tactics, including determination of the profile of patients requiring Tocilizumab prescription and the outcomes of MIS-C associated with COVID-19. Materials and methods of research: 245 children aged 3 months – 17 years old were included in the pilot prospective multicenter open-label comparative study with MIS-C associated with COVID-19, verified based on CDC criteria (2020). Results: the median age of patients was 8 [5; 10] years, boys predominated among the patients (57.1%); MIS-C manifested itself as a combination of the symptom complex of Kawasaki disease (KD, 53.1% of patients), more often of atypical form, cardiovascular (66.1%), gastrointestinal (61.2%), neurological (27.3%) symptoms and signs of detection of the urinary (29.4%) and respiratory (19.6%) systems; macrophage activation syndrome (MAS) was diagnosed in 19.5% of patients. Therapy included glucocorticosteroids (97.6%), antibiotics (95.5%), anticoagulants (93.9%), intravenous immunoglobulin (34.7%), vasoactive/vasopressor support (31.8%), Tocilizumab (15.1%), mechanical ventilation (2.4%), extracorporeal membrane oxygenation (0.4%). Patients receiving Tocilizumab, statistically significantly more often compared with patients without this therapy, were in the intensive care unit (ICU, 86.5% versus 40.9%, p<0.001), more often required vasopressor therapy (70.3% versus 25%, p<0.001), had statistically significantly higher markers of laboratory inflammatory activity. Treatment in 47.8% of cases was carried out in an ICU; one child has died. In 4.1%, according to echocardiography, coronaritis, ectasia of the coronary arteries without the formation of persistent aneurysms were detected. Conclusion: MIS-C associated with COVID-19 has clinical signs of KD, often of the incomplete form, accompanied by arterial hypotension/shock, MAS, which requires intensive therapy, and the prescription of Tocilizumab.

What’s “up”? Impaired Spatial Preposition Processing in Posterior Cortical Atrophy

This study seeks to confirm whether lesions in posterior regions of the brain involved in visuo-spatial processing are of functional relevance to the processing of words with spatial meaning. We investigated whether patients with Posterior Cortical Atrophy (PCA), an atypical form of Alzheimer’s Disease which predominantly affects parieto-occipital brain regions, is associated with deficits in working memory for spatial prepositions. Case series of patients with PCA and matched healthy controls performed tests of immediate and delayed serial recall on words from three lexico-semantic word categories: number words (twelve), spatial prepositions (behind) and function words (e.g., shall). The three word categories were closely matched for a number of psycholinguistic and semantic variables including length, bi-/tri-gram frequency, word frequency, valence and arousal. Relative to controls, memory performance of PCA patients on short word lists was significantly impaired on spatial prepositions in the delayed serial recall task. These results suggest that lesions in posterior parieto-occipital regions specifically impair the processing of spatial prepositions. Our findings point to a pertinent role of posterior cortical regions in the semantic processing of words with spatial meaning and provide strong support for modality-specific semantic theories that recognize the necessary contributions of sensorimotor regions to conceptual semantic processing.

Benzene poisoning

Benzene is a member of the aromatic hydrocarbon group and belongs to the group of blood poisons that cause inhibition of bone marrow hematopoiesis with the development of hypoplastic or aplastic anemia. The benzene can result in acute and chronic intoxication. Under industrial conditions, the penetration of benzene and its homologues into the human body is possible through the lungs and intact skin. The symptoms of changes in the nervous system and bone marrow hematopoiesis in acute and chronic exposure to benzene are different. Acute intoxication manifests itself with symptoms of damage to the central nervous system with the phenomena of general brain disorders, similar to poisoning with substances with narcotic properties. Chronic intoxication develops slowly, unnoticed by the patient, and is characterized by bone marrow damage with impaired blood cell formation. An atypical form of chronic benzene intoxication is the development of benzene leukemia. Therefore, benzene belongs to the group of industrial carcinogens. Typical forms of acute and chronic benzene intoxication are easy to recognize. To establish the diagnosis of benzene intoxication, it is necessary at first to have data confirming the patient’s contact with benzene. Repeated studies of peripheral blood, bone marrow puncture are important. There are no specific antidotes for benzene intoxication. Symptomatic treatment is performed only. Therefore, it is important to prevent the development of benzene intoxication in the workplace before the stage of deep irreversible disorders.

LEWIS-SUMNER SYNDROME: ANALYSIS OF ATYPICAL ONSET WITH PRIMARY ASYMMETRIC LESIONS OF LOWER LIMB NERVES

Lewis-Sumner syndrome is the most common atypical form of chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the disease is slowly progressive, which slows down the correct diagnosis. Timely diagnosis in some cases is also complicated by an abnormal primary lesion of the lower limb nerves in patients with Lewis-Sumner syndrome, for whom the typical clinical picture is upper flaccid distal paraparesis. The objective of the study is to determine the frequency of Lewis-Sumner syndrome (LSS), with the lower limb nerve onset; to characterize clinical and paraclinical characteristics of patients with the syndrome. Materials and Methods. The authors analyzed clinical data, results of stimulation electroneuromyography and ultrasound examination of peripheral nerves of 36 LSS patients. Results. The authors observed a high percentage (44 %) of LSS patients with lower limb nerve onset. However, changes in the neurophysiological and sonographic examination of the lower limb nerves, specific for CIDP, were not revealed. Changes typical of dysimmune neuropathy were verified only in the study of clinically intact long upper limb nerves. Conclusion. In asymmetric neuropathy of the lower limbs of idiopathic genesis, one should remember about LSS and, even despite the presence of symptoms only in the lower limbs, examine the peripheral nerves of the upper limbs. Key words: chronic inflammatory demyelinating polyneuropathy, Lewis-Sumner syndrome, atypical form. Синдром Льюиса – Самнера является наиболее частой атипичной формой хронической воспалительной демиелинизирующей полинейропатии (ХВДП). У большинства больных заболевание носит медленно прогрессирующий характер, что является одним из факторов увеличения сроков постановки верного диагноза. Своевременную диагностику в ряде случаев затрудняет и нехарактерное первичное поражение нервов ног у пациентов с синдромом Льюиса – Самнера, для которых типичной клинической картиной является верхний вялый дистальный парапарез. Цель исследования: определить частоту встречаемости синдрома Льюиса – Самнера (СЛС), дебютирующего с поражения нервов ног; охарактеризовать клинические и параклинические особенности больных с данным синдромом. Материалы и методы. Проанализированы клинические данные, результаты стимуляционной электронейромиографии и ультразвукового исследования периферических нервов 36 пациентов с СЛС. Результаты. Установлен высокий процент (44 %) встречаемости пациентов с СЛС с дебютом с поражения нервов ног. Однако специфические, характерные для ХВДП, изменения при нейрофизиологическом и сонографическом исследовании нервов ног не выявлены. Изменения, типичные для дизиммунной нейропатии, верифицированы только при исследовании клинически интактных длинных нервов рук. Выводы. В случаях асимметричной нейропатии нижних конечностей идиопатического генеза следует иметь настороженность в отношении СЛС и, даже несмотря на наличие симптоматики только в нижних конечностях, обследовать периферические нервы рук. Ключевые слова: хроническая воспалительная демиелинизирующая полинейропатия, синдром Льюиса – Самнера, атипичная форма.

Masqueraders: how to identify atypical diabetes in primary care

Diabetes mellitus is a complex set of conditions that impacts 34 million Americans. While type 1 diabetes, type 2 diabetes, and gestational diabetes are most frequently encountered, there are many other types of diabetes with which healthcare providers are less familiar. These atypical forms of diabetes make up nearly 10% of diabetes cases and can masquerade as type 1 or 2 diabetes mellitus (T1DM or T2DM), and the treatment may not be optimized if the diagnosis is not accurate. Atypical forms include monogenic diabetes (formally known as maturity-onset diabetes of the young [MODY]), latent autoimmune diabetes of the adult (LADA), ketosis-prone diabetes, and secondary diabetes. This paper will detail the defining characteristics of each atypical form and demonstrate how they can masquerade as type 1 or 2 diabetes mellitus. Gestational diabetes mellitus will not be discussed in this article.

Nonasthmatic Churg–Strauss syndrome superimposed on chronic pyelonephritis: a case report

Churg–Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient’s clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient’s chronic kidney disease finally progressed to dialysis dependence.