Unexplained Neurological Signs Research Articles

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

Hemorrhagic Brain Metastasis as an Initial Presentation of Hepatocellular Carcinoma in a Patient With Alcohol-Related Liver Cirrhosis: A Case Report and Review of Literature

Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer. Although it usually presents as a liver mass, rarely HCC can have an initial presentation at an extrahepatic site before the diagnosis of the primary lesion in the liver. Even rarely was that brain metastasis as initial extrahepatic presentations. Furthermore, the initial presentation of HCC as brain metastases has been with most cases being secondary to hepatitis-related hepatoma. In this case report, we are presenting a rare and unusual case of hemorrhagic cerebral metastasis as an initial extrahepatic presentation of an alcohol-related hepatoma. Our case is the second case in the English literature that has been presented in such a way. Due to the uncommonness of presentation, there can be diagnostic dilemmas and delay in treatment. Therefore, a high level of suspicion is needed in the high-risk patients of HCC who present with unexplained or new neurological signs and symptoms. More exploration is warranted for clinical research and treatment guidelines for brain metastases of HCC to help improve survival and quality of life.

Diagnostic utility of flow cytometric immunophenotyping in cerebrospinal fluid specimen

Abstract Introduction/Objective Flow cytometric immunophenotyping (FCI) of cerebrospinal fluids (CSF) has increasingly been used for diagnosing and monitoring hematologic malignancies. We reviewed CSF specimens sent for flow cytometry evaluation to identify the utility and limitations of FCI. Methods/Case Report We performed a retrospective review on CSF specimens received from July to October 2020. Samples were sent with requisition for unexplained neurologic signs or symptoms, to determine CNS involvement of neoplasm, or to stage a neoplasm. We reviewed specimen volume and cell count of flow cytometry samples and electronic medical records for possible diagnosis at time of specimen submission, final diagnosis, and concurrent cytology diagnosis. Results (if a Case Study enter NA) A total of 104 CSF samples from 59 patients were processed by the Flow Cytometry Laboratory during the review period. Of the 104 samples, 66% were from patients with a prior history of a hematologic malignancy, of which 20% had abnormal findings by FCI and cytomorphology. FCI was noncontributory for the cases in which patient did not have a previously diagnosed hematologic malignancy and underwent lumbar puncture for neurological abnormalities (n = 34). Concurrent cytology results were available in all but one case. Atypical or reactive findings by cytomorphology were seen in 21 cases (20%), for which flow cytometry studies showed no diagnostic immunophenotype in 12 cases. Abnormal FCI results occurred in 5 cases with history of hematologic malignancies, while concurrent cytomorphologic reports were negative. Conclusion Our findings suggest that CSF flow cytometry has low utility for screening patients with undifferentiated neurologic symptoms or without a prior hematologic malignancy history. Use as a screening tool for cases without clinical suspicion of hematolymphoid neoplasm is debatable. Flow cytometric and cytomorphologic analysis should be performed concurrently. While flow cytometric analysis in CSF may have higher sensitivity in hematologic malignancies, cytomorphology appears more favorable in identifying atypia or reactive conditions.

The Utility of Whole Exome Sequencing in Diagnosing Pediatric Neurological Disorders.

Pediatric neurological disorders have a wide spectrum of clinical presentations and can be challenging to diagnose. Whole exome sequencing (WES) is increasingly becoming an integral diagnostic tool in medicine. It is cost-effective and has high diagnostic yield, especially in consanguineous populations. This study aims to review WES results and its value in diagnosing neurological disorders. A retrospective chart review was performed for WES results between the period of January 2018 to November 2019. Whole exome sequencing was requested for children with unexplained neurological signs and symptoms such as epilepsy, developmental delay, visual impairment, spasticity, hypotonia and magnetic resonance imaging (MRI) brain changes. It was conducted for children in a pediatric neurology clinic of a tertiary center at Jeddah, Saudi Arabia. Twenty-six children with undiagnosed neurological conditions were identified and underwent WES diagnosis. Nineteen patients (73.0%) of the cohort were diagnosed with pathogenic variants, likely pathogenic variants or variants of unknown significance (VUS). Consanguinity was positive in 18 families of the cohort (69.0%). Seven patients showed homozygous mutations. Five patients had heterozygous mutations. There were six patients with VUS and six patients had negative WES results. Whole exome sequencing showed a high diagnostic rate in this group of children with variable neurological disorders.

Neurological complications of pandemic A(H1N1)2009pdm, postpandemic A(H1N1)v, and seasonal influenza A.

ObjectivesNot much is known about influenza‐associated neurological complications. We aimed to describe the case series of hospitalized patients who were confirmed with influenza A and presented with neurological symptoms in order to capture the broad spectrum of influenza clinical manifestation and suggest including influenza diagnostic in some neurological conditions.Materials and methodsThe inclusion criteria were age ≥ 18 and laboratory‐confirmed influenza presenting with neurological symptoms. Influenza‐associated neurological complication was described as a development of neurological symptom with no other origin. The outcomes were classified into 5 categories: 1. recovery with no significant disability; 2. minor disability (able to manage on their own); 3. moderate disability (requiring some help but able to walk without assistance); 4. severe disability (unable to walk without assistance and perform daily activities); 5. death.ResultsIn total, 12 patients (five women and seven men) were enrolled, with age range 18–71 years old. Neurological complications of pandemic A(H1N1)2009pdm influenza developed in seven out of 69 (10.1%) hospitalized patients. The most common neurological complication was encephalopathy. Neurological complications developed in two out of 24 (8.3%) hospitalized patients during postpandemic (H1N1)V period. One patient presented with encephalopathy, another with meningoencephalitis. During the 2018 influenza season, there was one patient who has developed influenza A neurological complications. Overall, two out of 104 (1.9%) influenza A patients developed influenza‐associated neurological complications in 2019.ConclusionsEvery patient with unexplained neurological symptoms and signs similar to aseptic and septic meningitis/encephalitis has to be tested for influenza virus during epidemics and pandemics.

Shuni Virus in Wildlife and Nonequine Domestic Animals, South Africa.

We screened nonequine animals with unexplained neurologic signs or death in South Africa during 2010–2018 for Shuni virus (SHUV). SHUV was detected in 3.3% of wildlife, 1.1% of domestic, and 2.0% of avian species. Seropositivity was also demonstrated in wildlife. These results suggest a range of possible SHUV hosts in Africa.

Viruses in Horses with Neurologic and Respiratory Diseases.

Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and a novel parvovirus) were detected in plasma from neurological cases. Plasma from horses with respiratory signs contained the same two copiparvoviruses plus equine pegivirus D and respiratory swabs contained equine herpes virus 2 and 5. Based on genetic distances the novel copiparvovirus qualified as a member of a new parvovirus species we named Eqcopivirus. These samples plus another 41 plasma samples from healthy horses were tested by real-time PCRs for multiple equine parvoviruses and hepacivirus. Over half the samples tested were positive for one to three viruses with eqcopivirus DNA detected in 20.5%, equine hepacivirus RNA and equine parvovirus-H DNA in 16% each, and horse parvovirus-CSF DNA in 12% of horses. Comparing viral prevalence in plasma none of the now three genetically characterized equine parvoviruses (all in the copiparvovirus genus) was significantly associated with neurological and respiratory signs in this limited sampling.

62-Year-Old Man With Back Pain and Lower Extremity Weakness

62-Year-Old Man With Back Pain and Lower Extremity Weakness

SCREENING OF EGYPTIAN PATEINTS SUFFERING FROM INBORN AMINO ACID METABOLIC DISORDERS

Diagnosis of aminoacidopathies constitutes a challenge in a developing country with high positive consanguinity rate and no newborn screening programs. The number of diagnosed inborn errors of amino acid metabolism is growing constantly due to the availability of recent analytical technique as tandem mass spectrometry (LC/MS/MS). This study highlights the importance of clinical awareness among physicians in patients presenting with unexplained neurological signs and alarming features that are commonly associated with metabolic diseases. Our scope is an assessment of overall prevalence rate of amino acid inborn errors metabolism in Genetics Research Unit, Pediatric Hospital, Ain shams University. Results indicate that 851 patients with phenylketonuria (PKU), 109 patients with maple syrup urine disease (MSUD), 15 patients with nonketotic hyperglycinemia (NKH), 14 patients with tyrosinemia, 4 patients with homocystinuria, 4 patients with citruillinimia and 3 patients with arginimia. It is clear that high consanguinity rate among families in different types of diseases that 1st cousin consanguinity is the highest rate among patients.

Autoimmune encephalitis.

Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides.

Conversion disorder in childhood presenting as movement disorder with severe injuries

Conversion disorder is characterized by the presence of one or more medically unexplained neurological symptoms and signs, which can manifest in all ages including children. In such cases, a stressor or conflict either initiates or exacerbates the condition. We present here a unique case of psychogenic movement disorder which was associated with injuries and when underlying stressors were identified, symptoms resolved with psychological treatment alone.

Detection of Circovirus in Foxes with Meningoencephalitis, United Kingdom, 2009-2013.

A fox circovirus was identified in serum samples from foxes with unexplained neurologic signs by using viral metagenomics. Fox circovirus nucleic acid was localized in histological lesions of the cerebrum by in situ hybridization. Viruses from the family Circoviridae may have neurologic tropism more commonly than previously anticipated.

Central Nervous System Involvement as Relapse in Undiagnosed Whipple's Disease with Atypical Symptoms at Onset.

Whipple’s disease (WD) is a rare systemic disease caused by the gram-positive bacillus Tropheryma Whipplei and mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.

PP15.8 – 2911: A rare cause of ptosis in four years old girl: Superior mediastinal malignant peripheral nevre sheath tumor

Objective The falling of the upper eyelid is called ptosis. It has been classified five mainly group as; myogenic, neurogenic, mechanical, aponeurotic and pseudoptosis. The symptoms occur at the same side as the lesion of the sympathetic trunk. Malignant peripheral nerve sheath tumors (MPNSTs) develop from Schwann cells, perineural cells and neural fibroblasts. MPNSTs are heavily homogeneous tumors consisting only of nerve sheath cells or Schwann cells. It can occur in any peripheral or cranial nerve. It develops mostly on the cranial nerves, autonomic nerves, and flexor sites of limbs. Methods We reported a rare presentation of MPNST with ptosis. Results A four year old girl admitted to our outpatient department of neurology with complaint of left ptosis for the last one month. Her neurologic examination was normal except ptosis and only one cafe au lait macule which are smaller than 1 cm were detected. There was no history of systemic illness or trauma, nor was any familial history obtained. Chest X-ray examination revealed a mass lesion in the lung. Chest MRI showed a 44×26×40 mm sized paravertebral mass at the level of C7-T1. She was diagnosed as sympathetic ptosis due to this mass. Abdomen CT, laboratory tests and bone marrow aspiration were normal. The lesion was surgically removed by thoracoscopic approach. The histopathological examination was relevant with MPNST. Conclusion To the best of our knowledge, there have been no previous reports of isolated ptosis as the initial presenting sign of MPNST. It is important to evaluate the chest X-ray presented with complaint of ptosis in children. We recommend that pediatricians and pediatric neurologists perform meticulous investigation in terms of neoplasm or paraneoplastic syndrome in newly developing, persisting, or unexplained neurological signs.

A Rare presentation of neurobrucellosis in a child with Recurrent transient ischemic attacks and pseudotumor cerebri (A case report and review of literature)

Brucellosis is a multi-system infectious disease that presents with various manifestations and complications. Neurobrucellosis is an uncommon but serious presentation of brucellosis that can be seen in all stages of the disease. High index of suspicion, especially in endemic areas is essential to prevent morbidity from this disease. The case was an 11- year -old female patient who was admitted with a severe headache that was worsening over a period of 2 months. The day after each attack, she experienced transient right hemiparesia that was lasting less than one hour (TIA) as well as blurred vision and bilateral papilledema. Laboratory findings revealed serum agglutination Wright test positive at 1/320 and 2ME test positive at 1/160. A lumbar puncture showed a clear CSF with increased opening pressure (32 cmH2O), CSF examination was within normal range (pseudotumor cerebri).To our knowledge, there has been no report for recurrent TIA in pediatric neurobrucellosis in the base of pseudotumor cerebri. In endemic areas like Iran, unexplained neurological signs or symptoms should be evaluated for brucellosis.

Importance of neuroimaging in children with presumed “cerebral palsy”: a brain tumour series: Abstract G10 Table 1

Aims Cerebral palsy (CP) is the term used to describe motor disorders resulting from a non-progressive insult to the developing brain. Presenting features may include disordered motor milestones or abnormal posture. Recommended pathways of investigation are based on a consensus of expert opinion. 1 All children in this case series presented with a motor disorder presumed to fall within the spectrum of CP but later confirmed to have a diagnosis of brain tumour. The authors therefore aim to support recent recommendations from the American Academy of Neurology (AAN) promoting the need for neuroimaging in all children with a descriptive label of CP. Methods Medical case notes were reviewed retrospectively from a series of children diagnosed with brain tumours who presented initially to community services with disorder in their motor development. The authors will present details of these nine cases (details in table 1), including one child with extreme prematurity. Time from onset of symptoms to diagnosis of tumour varied from 4 months to 3 years 2 months. These children did not undergo further investigation at the time of initial presentation and they were presumed to have CP. Discussion Brain tumours are the most common solid tumour in childhood and a significant cause of mortality and morbidity. Over 50% of children do not present with signs of raised intracranial pressure. 2 Symptoms and signs at presentation are variable and non-specific, including motor disorders or an abnormal motor developmental profile. A recent study reports MRI abnormalities in 84% of children with CP, 3 but findings are often non-specific and may not establish aetiology. 4 The AAN recommends neuroimaging using MRI in all cases of suspected CP with unknown aetiology. Conclusion This case series highlights the danger of applying an assumed explanation with the term CP, highlighting the importance of a detailed history and thorough examination during assessment. Prompt neuroimaging should be considered in all children with unexplained neurological symptoms or signs. Early diagnosis of malignancy is now a defined UK strategy. As in other malignancies, prompt recognition of brain tumours may help in the prevention of their significant associated morbidity.

Carcinomatous meningitis from adenocarcinoma of the uterine cervix: A case report and literature review

Carcinomatous meningitis from uterine cervix-related malignancies is a rare complication. We found only eight cases of meningeal metastasis from primary cervical carcinoma in the English-language medical literature. However, its incidence has increased recently, probably because carcinomatous meningitis is being identified more often and survival time for the primary disease is extended. Thus, the clinical signs and methods for diagnosis are of great importance. A 47-year-old Japanese woman had a stage IIIb uterine cervical adenocarcinoma. She chose initial chemotherapy followed by radical hysterectomy and adjuvant chemotherapy. Ten months after initial chemotherapy and 6 weeks after the last chemotherapy, she suddenly presented with unexplained neurological signs. We performed a lumbar puncture, which demonstrated adenocarcinoma cells compatible with metastases from the primary cervical adenocarcinoma. She died 7 weeks later. This rare complication occurs in the advanced stage of cervical cancer. Lumbar punctures for neoplastic cells are advised, and the prognosis remains poor.

Cerebrospinal Fluid Neopterin and Cryopyrin-Associated Periodic Syndrome

Cryopyrin-associated periodic syndrome is a category of autoinflammatory disorders caused by mutations of the NLRP3 gene, with chronic infantile neurologic cutaneous and articular syndrome being the severest clinical phenotype. Various pterins have been reported as mediating immunologic functions in the central nervous system, but to date studies of pterin cerebrospinal fluid (CSF) values and cryopyrin-associated periodic syndrome have been lacking. A 2-year-old child was affected with a severe atypical form of cryopyrin-associated periodic syndrome, suspected based on the analysis of neopterin in CSF. He initially presented isolated neurologic manifestations mimicking a neuroregressive disorder. Blood and CSF analyses did not present any routine inflammatory markers, but CSF neopterin was elevated. Later, the patient developed arthritis and recurrent episodes of fever, and the cryopyrin-associated periodic syndrome diagnosis was confirmed by genetic studies. Neopterin was the most altered indicator over the time. Child neurologists should be on the alert when unexplained neurologic signs appear, giving consideration to the possibility of inflammatory or immune-mediated diseases. The present case demonstrates the clinical utility of measurement of CSF neopterin levels in screening for these immune-mediated diseases, especially when neurologic symptoms are associated with normal results on routine CSF tests.

Lineage 2 West Nile Virus as Cause of Fatal Neurologic Disease in Horses, South Africa

Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-PCR) and immunoglobulin (Ig) M ELISA, we found WNV RNA or IgM in 7/32 horses with acute neurologic disease; 5 horses died or were euthanized. In 5/7 horses, no other pathogen was detected. DNA sequencing for all 5 RT-PCR-positive cases showed the virus belonged to lineage 2. WNV lineage 2 may cause neurologic disease in horses in South Africa.

Progressive multifocal leucoencephalopathy in the rheumatic diseases: assessing the risks of biological immunosuppressive therapies

Progressive multifocal leucoencephalopathy (PML) is a rare and often fatal opportunistic infection that has been well reported in patients with rheumatic diseases. The contributions of predisposing factors such as underlying...