Central Neurological Manifestations Research Articles

Wernickeʼs Encephalopathy Following Roux-en-Y Gastric Bypass Complicated by Gastrojejunal Stenosis and Small Bowel Obstruction: 2016 ACG Presidential Poster Award

A 28 year-old woman was admitted to our hospital with 3 weeks of abdominal pain, nausea, and vomiting. At another facility, she had undergone Roux-en-Y gastric bypass 3 months prior for morbid obesity, followed by laparoscopic cholecystectomy one week prior for presumed chronic cholecystitis. The patient suffered from multiple daily episodes of nausea and vomiting, resulting in a 95 pound weight loss since her bariatric surgery. The cholecystectomy did not improve her symptoms. Neurologic examination was remarkable for horizontal rotary nystagmus, patellar and ankle areflexia, impaired pin-prick and temperature sensation of anterior aspects of the chest and abdomen, as well as distal legs and feet, impaired vibration sense in both feet, and wide-based ataxic gait. Empiric high dose intravenous thiamine repletion was immediately begun; whole blood thiamine level was later confirmed to be low. An upper GI series/small bowel follow-through did not reveal an obstruction initially, though CT scan showed a distended and fluid-filled gastric remnant and proximal small bowel, with possible transition point near the jejunojejunal anastomosis. EGD, however, demonstrated a normal appearing jejunojejunal anastomosis, but a mild gastrojejunal stenosis, which was successfully dilated. The patient rapidly improved following the dilation and with aggressive thiamine repletion. However, she was re-admitted three weeks later with recurrence of pain, nausea, and vomiting. CT now showed an evolving small bowel obstruction, prompting exploratory laparotomy with lysis of an adhesive band causing obstruction of the common channel. A feeding gastrostomy tube was also placed. Her neurological signs and symptoms have since improved and she is no longer requiring tube feeds. This case illustrates the importance of prompt attention to the development of any central or peripheral neurologic manifestations following bariatric surgery. This is especially important for thiamine deficiency, as Wernicke's encephalopathy only rarely presents with the classical triad of altered mental status, ocular motility abnormalities, and ataxia. If Wernicke's encephalopathy is suspected, it should be treated urgently, as confirmatory laboratory results would result in delays during which neurologic damage may progress. Additionally, although gastric bypass itself can predispose to thiamine deficiency, an underlying etiology, such as complications of surgery, should be sought and addressed.Figure 1Figure 2Figure 3

Epidemiology of neurological manifestations in Sjögren's syndrome: data from the French ASSESS Cohort

ObjectivesNeurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort...

Non-stroke Central Neurologic Manifestations in Antiphospholipid Syndrome.

Thrombotic manifestations of antiphospholipid syndrome (APS) are well known, and various non-stroke neuro-psychiatric manifestations (NPMs) have also been consistently described, but their place in APS remains unclear. Some syndromes, such as migraine or cognitive dysfunction, are frequently described in APS, whereas others, like seizure, multiple sclerosis-like symptoms, transverse myelitis, movement disorders, or psychiatric symptoms, are rarely found. Overlap with other autoimmune diseases, in particular with systemic lupus erythematosus, the lack of large sample size prospective studies, and discrepancies in antiphospholipid antibody (aPL) determinations complicate the study of the relationship between those disorders and aPL/APS. This review article aimed to summarize updated data on pathophysiologic, epidemiologic, and radiologic findings about non-stroke NPM described in primary APS and aPL-positive patients without overlap of other autoimmune diseases.

Coma myxœdémateux et syndrome cérébelleux révélateurs d’un syndrome de Sheehan

Sheehan's syndrome (SS) or postpartum pituitary necrosis corresponds to a complete or dissociated hypopitui- tarism, usually precipitated by a brutal or prolonged hemor- rhagic shock during the delivery. This condition has become rare in developed countries while it is probably fairly fre- quent in our country despite the improvement of obstetric conditions. The case reported concerning a young woman of 29 years admitted with an array of acute adrenal insufficiency associated with myxedema coma, neurological disorders involving a cerebellar syndrome, and peripheral neuropathic syndrome, reveals Sheehan syndrome. The clinical course turns rapidly with specific hormone. Acute and severe clinical forms of SS are rare. Acute adrenal insufficiency is the mode by which most acute revelation is described, while myxe- dema coma remains exceptional. The central and peripheral neurological manifestations of hypopituitarism are known. Although it is rare that these neurological symptoms indicate thyrotropic insufficiency, the central hypothyroidism should not be disregarded as replacement therapy usually provides a spectacular clinical evolution.

Nevus Comedonicus Syndrome.

A case of nevus comedonicus syndrome with atypical cutaneous presentation (widespread involvement without any particular pattern, midline lesions involving lower abdomen and involvement of bilateral pinna), and some unusual skeletal (adduction deformity involving bilateral metatarsal along with medial deviation at the level of tarsometatarsal joint), central nervous system (agenesis of corpus callosum with a interhemispheric cyst), visceral (pancreatic cyst) and neurological manifestations have been illustrated.

Hernie discale thoracique

The reported incidence of thoracic disk herniation is closely dependent on the imaging methods used for the diagnosis. Nevertheless, thoracic disk herniation is very rarely symptomatic. Fewer than 2 % of all surgical procedures for disk disease involve the thoracic spine. The clinical presentations may be misleading. A thorough neurological evaluation is necessary to identify the frequently subtle abnormalities, particularly those indicating involvement of the long tracts. This variability in the clinical manifestations may be ascribable not only to direct compression, but also to concomitant blood supply impairment. Nonsurgical treatment may be an option in patients without central neurological manifestations. Otherwise, surgery should be considered after extensive imaging studies and an assessment of feasibility, in order to allow detailed planning of the surgical procedure. Several techniques are available. Isolated laminectomy should not be performed. Costotransversectomy, thoracoscopy, and video-assisted minimally invasive thoracotomy are currently the most widely used methods. Anterior approaches may provide better outcomes in patients with midline calcified disk herniations, by limiting the need for spinal cord mobilization.

Beyond the joints

Although arthritis is the most notable component, rheumatoid arthritis (RA) is a systemic inflammatory disorder where extra-articular manifestations are common; among them, central and peripheral nervous system involvement is frequent and associated with significant morbidity and, in some cases, reduced life span. It may produce a myriad of symptoms and signs ranging from subtle numbness in a hand, to quadriparesis and sudden death. Central and peripheral neurologic manifestations may arise from structural damage produced by RA in diarthroidal joints, by the systemic inflammatory process of the disease itself or by the drugs used to treat it. Neurologic syndromes may appear suddenly or developed slowly through months, and emerge early or after years of having RA. Neurologic manifestations may be easily overlooked or incorrectly assigned to peripheral arthritis unless the attending physician is aware of these complications. In this article, we review neurologic involvement in RA patients with emphasis on clinical approach for early detection.

Microscopic polyangiitis presenting with peripheral and central neurological manifestations

Although peripheral neuropathy is a common complication of microscopic angiitis, manifestations involving the muscle and the central nervous system have been rarely reported. We describe a 48-year-old man who rapidly developed a clinical picture of mononeuritis multiplex. A month after the appearance of the primary symptoms, he became comatose and had left hemiplegia in relation with a massive cerebral haematoma. Laboratory data revealed signs of inflammation, glomerular dysfunction with microhaematuria, and positive myeloperoxidase-antineutrophil cytoplasmic antibodies. The neuromuscular biopsy disclosed a small-vessel vasculitis, consisting with microscopic angiitis, associated with myositis and extensive axonal loss. The patient had surgical evacuation of the haematoma and received immunosuppressive therapy with good outcome. Thus, microscopic angiitis should be considered as a differential diagnosis in cases of myositis and intracerebral haemorrhage.

Pachyméningite crânienne et syndrome de Gougerot-Sjögren primitif

Central neurological manifestations of primary Sjogren's syndrome are very polymorphic, including pachymeningitis, one of the rarest manifestations, which is exceptionally inaugural. A 50-year-old patient was admitted for an intracranial hypertension syndrome with paralysis of the III and VII cranial nerves. Brain MRI revealed pachymeningitis of the right cerebral hemisphere. History taking revealed the existence of xerostomy and xerophthalmos. The accessory salivary gland biopsy demonstrated Chisholm stageIII sialadenitis. Search for anti-SSA antibodies and anti-SSB antibodies was positive. The diagnosis of primary Sjogren's syndrome was retained. The patient improved with corticosteroid therapy and cyclophosphamide. This case illustrates the unusual observation of pachymeningitis in primary Sjogren's syndrome in the rare setting as an inaugural manifestation.

Cognitive impairment and McArdle disease: Is there a link?

McArdle disease is caused by deficiency of myophosphorylase, the muscle isoform of glycogen phosphorylase. This isoform is also expressed in astrocytes, where it seems to have a key role in neural energy metabolism. Whereas in other glycogen storage diseases cognitive impairment has been rarely reported, it has not been previously observed in McArdle disease. Here we report the case of an Italian 55-year-old woman with McArdle disease and cognitive impairment with bilateral dysfunction of prefrontal and frontal cortex (shown by neuropsychological assessment and fluorodeoxyglucose PET). Further studies are needed to assess the prevalence of central neurological manifestations in this disease.

Utility of Serum S100B Protein for Identification of Central Nervous System Involvement in Systemic Lupus Erythematosus

To evaluate utility of S100B protein in serum as a marker of central nervous system involvement in systemic lupus erythematosus (SLE). Forty patients with SLE, hospitalized because of central neuropsychiatric (cNP) manifestations (n = 36) and peripheral NP manifestations (pNP, n = 4) were studied. Patients were evaluated at hospitalization and 6 months later, including a serum and cerebrospinal fluid (CSF) sample. As controls, 4 SLE patients with septic meningitis (SLEsm), 13 surgical SLE patients (SLE surgical), 14 patients with nonautoimmune diseases, and 4 patients with primary NP syndromes were included. Serum and CSF S100B protein levels were determined by ELISA. At baseline, serum levels of S100B protein did not differ across SLE groups. Using an arbitrary cutoff value, positive S100B levels in serum were observed in 7 (19%), 6 (46%), and 1 patient from the cNPSLE, SLE surgical, and SLEsm groups, respectively. S100B protein levels in cNPSLE and SLE surgical patients were similar. In CSF, S100B protein levels did not differ among SLE groups, except in patients with SLEsm. Paired serum/CSF samples were obtained in 23 patients with cNPSLE at 6 months after the acute event. Overall, levels of S100B protein in serum did not change despite the decrease observed in CSF (p = 0.004). The correlation coefficient of serum and CSF S100B protein levels among all the SLE patients at baseline was poor (r = 0.23). Serum levels of S100B protein do not differentiate SLE patients with and those without central neurological manifestations.

Beware of chest wall lesions

Sir, Neurofibromatoses (NF) are genetically and clinically distinct neurocutaneous disorders, inherited in an autosomal dominant fashion. The two key types comprise 95% of patients with NF and are classified as types 1 (NF1 or von Recklinghausen's disease) and 2 (NF2 or MISME syndrome), the latter being significantly rarer than the former. NF1 has a predilection for cutaneous and peripheral nervous pathologies, whereas NF2 is characterized by central neurological manifestations, notably vestibular schwannomas. We report a case of a large neurofibroma involving the pleura in a 14-year-old male who was referred to a plastic surgeon in 2009 for excision of a hemispherical soft wellcircumscribed very slowly enlarging, but otherwise asymptomatic subcutaneous lesion on the anteroinferior part of the chest wall (Fig. 1). This patient was fit and healthy and had not had any similar lesions. Due to its size, location and history, imaging was undertaken. Magnetic resonance imaging revealed a well-defined flattened oval, enhancing 3 cm subcutaneous lesion intimately related to the left anterior thoracic wall and extending through the intercostal muscles to reach the pleura. Imaging characteristics were suggestive of a neurofibroma. The lesion was placed under surveillance and not excised as there were no significant symptoms, such as pleuritic pain consequential to it. Had surgery without imaging taken place, a risk of major haemorrhage would have been a possibility secondary to excision-related laceration to the pleura or injury to intercostal vessels. NF1 can involve the lung with pulmonary fibrosis occurring to a variable degree in approximately 10% of patients. Other complications include respiratory failure due to spontaneous haemothorax [1, 2] and intrathoracic meningocoele [3] leading to pleural effusions. Cases of localized and diffused pleural neurofibromas have been described [1, 4], albeit very infrequently. In the former, chest roentgenogram and CT scan results adequately demonstrated the lesion. A pleural neurofibroma should be considered as a differential diagnosis for similarly located lesions, and imaging with biopsy, if possible, for nuclear and immunohistological staining should be undertaken to distinguish it from solitary fibrous tumours—the most common localized pleural tumour. Indeed, a new diagnosis of NF1 can potentially be made in such a manner (Figs. 2, 3, 4). I hereby confirm that all authors have been actively involved in the planning and preparation of this article and that this article has not been submitted elsewhere. References have been checked using Pubmed. Should this submission be accepted for publication in this journal, this manuscript shall not be published elsewhere in the same or similar form, in English or in any other language without written consent of the copyright holder. The corresponding author has the right to grant on behalf of all the authors and does grant on behalf of all the authors, an exclusive licence on a worldwide basis to the publisher and its licensees to use this article with appropriate accreditation. N. Sivathasan :G. Ansede :K. H. Chakrabarty Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK

Hydrocephalus and Chiari type 1 malformation in macrocephaly-cutis marmorata telangiectatica congenita: a case-based update

Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is a newly described condition characterized by macrocephaly (megalencephaly), cutis marmorata telangiectatica congenita, macrosomia and/or asymmetric growth, central nervous system abnormalities and neurological manifestations. This condition is usually documented in the Genetics' literature but it has been scarcely disseminated among neurosurgeons. Sudden death of uncertain origin has been reported in children with M-CMTC. Hydrocephalus and tonsillar herniation often occur in this syndrome. The appearance of symptoms and signs of intracranial hypertension or of brain stem compression in M-CMTC patients may herald the development of irreversible neurological damage or death. We report two children diagnosed with M-CMTC and hydrocephalus who were given a ventriculo-peritoneal shunt. In addition, one of them exhibited tonsillar herniation. Given the high incidence of hydrocephalus and/or tonsillar herniation that occurs in M-CMTC, serial neuroimaging studies and neurosurgical referral seem to be warranted in children with this syndrome.

Fronto-orbital sphenoethmoidal fibrous dysplasia

Cranial fibrous dysplasias (FDs) are rare and comprise less than 1% of all primary bone lesions. They may produce cosmetic deformities, peripheral compressive cranial neuropathies, and compressive central neurologic manifestations. We describe an unusual presentation of a fronto-orbital sphenoethmoidal FD in a 32-year-old woman with conventional radiographic, CBCT, and MRI findings. In the head and neck examination, an asymmetry was noticed on the left side, without evidence of adenopathy, paresthesia, or motor nerve deficiency. Panoramic radiographs showed a radiopaque expanded bone in the region of the posterior maxillary sinus and orbita. Computed tomography with three-dimensional reconstruction demonstrated an expanding lesion of the cranial bones, involving the ethmoid and periorbital bone, producing a ground-glass appearance. After the radiologic examination, the patient was referred for surgery with a diagnosis of cranial FD and underwent a cranioplasty. The CT and MRI features were typical for FD, but physicians and dental professionals should be aware of this diagnosis, even if no symptom is apparent and the patient came in only for a routine dental examination. Maxillofacial radiologists should also consider that the signal intensity on both T1- and T2-weighted images and the degree of contrast enhancement on T1-weighted images depend on the amount and degree of bony trabeculae, cellularity, collagen, and cystic and hemorrhagic changes.

Maladie de Whipple

Whipple's disease is a chronic, multisystemic, curable, bacterial infection that usually affects middle-aged men. It has a wide range of clinical manifestations. In the historical presentation, weight loss and diarrhoea are the most common symptoms and are preceded in three-quarters of cases by arthritis for a mean of six years. Long-term, unexplained, seronegative oligoarthritis or polyarthritis of large joints with a palindromic or relapsing course is typical. In most patients, periodic acid-Schiff staining of proximal small bowel biopsy specimens reveals inclusions within the macrophages, corresponding to bacterial structures. However, patients may have no gastrointestinal symptoms, negative jejunum biopsy results and even negative PCR tests. Even in the absence of gastrointestinal symptoms, Whipple's disease should be considered in case of negative blood culture endocarditis, unexplained central neurological manifestations or unexplained arthritis. Identification of the causative bacterium, Tropheryma whipplei, has led to the development of PCR as a diagnostic tool, particularly useful in patients in the early stages of the disease or with atypical disease. The recent cultivation of T. whipplei and the complete sequencing of its genome should improve our understanding and treatment of the disease. The future development of an assay for detection of specific antibodies in the serum and generalization of the immunohistochemical detection of antigenic bacterial structures may allow earlier diagnosis, thereby preventing the development of the severe late systemic and sometimes fatal forms of the disease.

Manifestations neurologiques des maladies inflammatoires chroniques de l’intestin

Introduction Several extra-intestinal manifestations of inflammatory bowel disease have been reported, although reports of neurologic disorders are rare. Case reports We report two cases of peripheral and central neurological manifestations of inflammatory bowel disease. The first case is a 33-year-old woman who developed acute inflammatory demyelinating motor polyneuropathy in association with Crohn's disease. Her symptoms improved with immunomodulatory therapies. Our second case is a 46-year-old woman, previously diagnosed with ulcerative colitis that subsequently developed ischemic stroke concomitantly to severe exacerbation of digestive symptoms. Her radial and humeral pulses were unequal bilaterally. Associated Takayashu's arteritis was suspected. The cardiovascular and immunological assessments were negative. Complementary investigations were foreseen but the patient died early of acute abundant rectal bleeding. Conclusion This paper focuses essentially on the probable manifestations of inflammatory bowel disease in the nervous system, particularly peripheral neuropathies and stroke. We discuss different pathophysiologic mechanisms incriminated, notably thromboembolism and immunological abnormalities.

Syndrome cérébelleux isolé révélant un syndrome de Gougerot-Sjögren primaire

Primary Sjogren's syndrome is an autoimmune exocrinopathy with various extraglandular complications. Central neurological manifestations were described in 20 percent of cases. Cerebellar syndrome is uncommon in Sjogren's syndrome, but can occur after diagnosis, or rarely as an inaugural sign of the disease. We report the case of a 54-year-old man who presented a cerebellar syndrome with xerostomy and xerophthalmos. The diagnosis of primary Sjorgren's syndrome was confirmed on the accessory salivary gland biopsy. The patient received oral and intravenous corticosteroid therapy associated with cyclophosphamide monthly. Outcome was good.

Specific antibody index in cerebrospinal fluid from patients with central and peripheral paraneoplastic neurological syndromes

We evaluated the concentration of antineuronal antibodies in paired cerebrospinal fluid (CSF) and serum samples from 19 patients with central and peripheral paraneoplastic neurological syndromes (PNS), using an enzyme linked immunosorbent assay (ELISA) employing recombinant antineuronal antigens (HuD, Yo, Ri, CV2/CRMP5, amphiphysin, PNMA2/Ma2). The specific antibody index (AI) [ Q spec/ Q IgG] was calculated to estimate specific intrathecal antibody synthesis. An AI > 1.3 was considered as evidence of intrathecal specific antibody synthesis. 14 (88%) of 16 patients with exclusive or predominant paraneoplastic involvement of the central nervous system (CNS) showed an AI > 1.3, indicating a specific intrathecal antibody synthesis, while all three patients with isolated involvement of the peripheral nervous system showed an AI < 0.8. All together, in 17 of 19 patients (89%) we found a significant association ( p < 0.05) between central or peripheral neurological manifestations on the one hand and presence or absence of specific intrathecal synthesis respectively on the other hand. These data support the hypothesis that autoimmunity is involved in the pathogenesis of PNS.

α- l-Iduronidase transport in neurites

Effective therapeutic strategies for mucopolysaccharidosis type I (MPSI) rely on mannose-6-phosphate receptor-mediated uptake of extracellular α- l-iduronidase (IDUA), the missing lysosomal enzyme in this disease, by deficient cells. Intravenously infused recombinant human IDUA does not reach the central nervous system, whereas neuropathology and neurological manifestations are prominent in Hurler syndrome, the most severe and most frequent form of MPSI. The creation of a single intracerebral source of IDUA by gene therapy was proved efficient to deliver enzyme throughout the brain of MPSI mice. IDUA spreading far beyond areas where the enzyme was synthesized suggested transport along neuronal processes. To examine the mechanisms of IDUA spreading in the brain, we constructed a chimeric protein in which GFP is fused at the C-terminus of IDUA. The fusion protein was expressed in rat primary neurons using lentivirus vectors. Fluorescent IDUA retained full catalytic activity including on natural substrates, interacted with mannose-6-phosphate receptors and was appropriately addressed to lysosomes. Fluorescent vesicles were broadly distributed over neuronal soma and processes. Time-lapse fluorescent video-microscopy showed that 54% of fluorescent vesicles exhibited either retrograde or anterograde displacements along neurites. Most moving organelles showed complex movements with frequent direction changes and arrests. Motility depended on microtubule integrity. Efficient axono-dendritic transport of IDUA provides a rationale for gene therapy based on the release of therapeutic enzyme at discrete locations within the central nervous system of patients with severe form of MPSI.

Acute Intermittent Porphyria

Acute intermittent porphyria (AIP), due to half-normal hydroxymethylbilane synthase activity,is characterized by acute life-threatening neurologic attacks whose etiology remains unclear. To date, only 3 patients confirmed to have homozygous dominant AIP (HD-AIP) have been described (hydroxymethylbilane synthase genotypes R167Q/R167Q and R167W/R173Q). To investigate the genetic, biochemical, clinical, and neuroradiologic features of a severely affected infant with HD-AIP. Clinical, imaging, and genotype/phenotype studies were performed. The proband, homoallelic for hydroxymethylbilane synthase mutation R167W, had approximately 1% of normal hydroxymethylbilane synthase activity, elevated porphyrins and porphyrin precursors, severe psychomotor delay, and central and peripheral neurologic manifestations. When expressed in vitro, the R167W mutant enzyme had less than 2% of normal activity but was markedly unstable, consistent with the proband's severe phenotype. Mitochondrial respiratory chain enzymes were normal. Neuroradiologic studies revealed a unique pattern of deep cerebral white matter injury, with relative preservation of the corpus callosum, anterior limb of the internal capsule, cerebral gray matter, and infratentorial structures. This severely affected patient with HD-AIP expanded the phenotypic spectrum of HD-AIP. His brain magnetic resonance imaging studies suggested selective cerebral oligodendrocyte postnatal involvement in HD-AIP, whereas most structures developed prenatally were intact. These findings indicate that the neurologic manifestations result from porphyrin precursor toxicity rather than heme deficiency and suggest that porphyrin precursor toxicity is primarily responsible for the acute neurologic attacks in heterozygous AIP and other porphyrias.