Clinically confirmed tuberculous radiculomyelitis: a case report

A Seven-Month-Old Infant With Acute Onset of Neurologic Deterioration

Intrathecal Bleeding After the Intraoperative Use of Heparin and Urokinase During Continuous Spinal Anesthesia

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of various diseases, including trigeminal neuralgia, neuropathic pain and psychiatric disorders, particularly bipolar depression [1]. Carbamazepine adverse reactions range from minimal, dose-dependent central nervous system effects to severe, irreversible bone marrow depression, as well as idiosyncratic reactions and allergic reactions, including Stevens–Johnson syndrome and hypersensitivity syndrome. We report a patient with a 2-year history of epilepsy treated with carbamazepine who developed urinary retention under carbamazepine therapy. Urinary symptoms disappeared when carbamazepine was discontinued. A 38-year-old women, with a 2-year history of epilepsy treated with carbamazepine (200 mg twice daily), came to the emergency room because of lower abdominal discomfort and inability to void. Three days earlier she had started to complain of urgency and dribbling of urine, and then developed acute urinary retention. She reported a history of urgency, hesitancy, dribbling of urine and poor stream which began shortly after carbamazepine initiation and which she tolerated for almost 2 years without seeking medical care because of shame. She denied any previous history of haematuria, urological or gynaecological intervention. Clinical examination revealed suprapubic tenderness without guarding or rebound, suggestive of distended bladder. A urinary catheter was immediately inserted and drained 1100 ml of clear urine. Pelvic and gynaecological examinations were normal. She was apyrexial and without any other physical finding. Kidney function tests, complete blood count, glucose, albumin, sodium and potassium serum concentrations were within normal range. Urine cell count and urine chemistry were normal. Urine culture was negative. Abdomen plain X-ray and ultrasound were normal. Mechanical obstruction was ruled out by normal pelvic, genitourinary and rectal examinations. The origin of this acute urinary retention was initially intriguing, but when, subsequently, the patient reported a dry mouth with flushing and dryness of the skin that appeared several days after carbamazepine initiation, a drug-induced event seemed the most likely origin of the voiding symptoms. Carbamazepine was the only medication with anticholinergic properties taken by the patient, and the most likely causal agent. Although the carbamazepine serum concentration was 11 µg/ml (therapeutic range 4–12 µg/ml) it was withdrawn and replaced by valproic acid. Voiding symptoms and anticholinergic features did not recur over a 12-month follow-up period. Carbamazepine-induced urinary retention has been reported in the literature, but in most of the cases there was evidence of underlying disease such as longstanding diabetes mellitus with severe peripheral neuropathy in two patients [1], and Fabry's disease with autonomic dysfunction in two others [2]. It is obvious that carbamazepine might have interfered with these conditions and precipitated acute urinary retention. Therefore, these contributing factors might have biased the causality relationship between urinary retention and carbamazepine. In addition, the male gender of the patients previously reported and their advanced age raise questions about a possible prostatic contribution to the abnormalities in voiding. Fowler's syndrome represents the main differential diagnosis in our patient, but its clinical picture and natural history are completely different [3]. In our case, there are five arguments against this syndrome. First, voiding symptoms began within a few days following initiation of carbamazepine, and disappeared completely after discontinuation of the drug. Second, the urethral sphincter on the anterior vaginal wall was not enlarged on palpation. Third, the urge to void has never disappeared, and the retention of urine was painful, facts that argue for the persistence of bladder filling sensation, in contrast to Fowler's syndrome, in which the sensationof bladder filling is suppressed. Fourth, symptoms of Fowler's syndrome do not resolve spontaneously and usually require specific therapy. Fifth, anticholinergic symptoms have no reason to occur in Fowler's syndrome. Our case adds credence to previous reports of carbamazepine-induced urinary retention. Indeed, an objective causality assessment using the Naranjo rating scale has revealed that the adverse drug event was probable [4]. In addition, in contrast to previously reported cases, the female gender of our patient excluded from the start the hypothesis of prostatic-related urinary disturbances. Normal pelvic, genitourinary and rectal examinations, as well as normal medical imaging results, ruled out the possibility of mechanical obstruction of the bladder due to extrinsic compression. The absence of autonomous nervous system involvement in our patient is another difference from previously reported cases. The exact mechanism of carbamazepine-induced urinary retention is not well elucidated. However, the well-known chemical relation between carbamazepine and tricyclic antidepressants may explain the occurrence of anticholinergic effects. It is thought that urinary retention due to anticholinergics is secondary to their inhibitory effect on bladder contraction in predisposed patients, particularly in the presence of outlet obstruction and autonomic nervous system dysfunction. This effect results from antagonizing postjunctional excitatory muscarinic receptors M2 and M3 in the detrusor muscle of the bladder interfering with bladder contraction and emptying, thereby facilitating urinary storage and retention [5]. If not recognized and reversed early on, this condition can lead to urinary tract infection and damage to the kidneys [6]. The reversibility of carbamazepine-induced urinary retention by the cholinergic agent bethanecol in a previous report supports the presumed anticholinergic mechanism of this drug adverse event [1]. Carbamazepine has also been reported as a cause of overflow urinary incontinence [6, 7] and has been proposed to treat primary nocturnal enuresis [8]. Even though a rare drug adverse event, carbamazepine-induced urinary retention should be recognized not only in predisposed patients but also under normal circumstances. The authors thank Mr Hédi Amamou for his invaluable support.

Despite the efficacy of highly active antiretroviral treatment (HAART), a large proportion of human immunodeficiency virus (HIV)-infected patients may develop moderate neurocognitive impairment. Antiretroviral drug passage into the central nervous system may be relevant for preventing and treating HIV-associated neurocognitive disorder; nevertheless, clear cerebrospinal fluid (CSF) pharmacodynamic targets are not known. HAART-treated adults with wild-type HIV were prospectively enrolled. CSF concentrations (measured by mass spectrophotometric methods) and inhibitory quotients (CSF concentrations divided by in vitro 50% and 95% inhibitory concentrations) were compared among different drugs and related to CSF HIV RNA levels. CSF escape was defined as CSF HIV RNA >50 copies/mL despite contemporary plasma HIV RNA below that threshold. One hundred twenty-seven patients (91 male [71.7%], 93 white [73.2%], with a median age of 46 years [interquartile range, 40.5-54.5 years]) provided 174 paired CSF and plasma samples. Twice-daily darunavir, once-daily darunavir, and efavirenz had the highest CSF 95% inhibitory quotients (18.5, 8.2, and 6.4, respectively). Higher nadir CD4 cell count (P = .01) and plasma HIV RNA <50 copies/mL (P < .001) were independent predictors of controlled CSF HIV RNA. Optimal drug exposure (CSF detectable drugs and 95% inhibitory quotient >1) was protective for CSF escape (P = .01). Cerebrospinal fluid 95% inhibitory quotients may be used to compare antiretroviral drug compartmental exposure; they deserve longitudinal studies to assess the adequacy of CSF drug concentrations in treated HIV-infected patients.

To review infectious diseases that may cause autonomic dysfunction. Review of published papers indexed in medline/embase. Autonomic dysfunction has been reported in retrovirus (human immunodeficiency virus (HIV), human T-lymphotropic virus), herpes viruses, flavivirus, enterovirus 71 and lyssavirus infections. Autonomic dysfunction is relatively common in HIV-infected patients and heart rate variability is reduced even in early stages of infection. Orthostatic hypotension, urinary dysfunction and hypohidrosis have been described in tropical spastic paraparesis patients. Varicella zoster reactivation from autonomic ganglia may be involved in visceral disease and chronic intestinal pseudo-obstruction. Autonomic and peripheral nervous system dysfunction may happen in acute tick-borne encephalitis virus infections. Hydrophobia, hypersalivation, dyspnea, photophobia, and piloerection are frequently observed in human rabies. Autonomic dysfunction and vagal denervation is common in Chagas disease. Neuronal depopulation occurs mainly in chagasic heart disease and myenteric plexus, and megacolon, megaesophagus and cardiomyopathy are common complications in the chronic stage of Chagas disease. Parasympathetic autonomic dysfunction precedes left ventricle systolic dysfunction in Chagas disease. A high prevalence of subclinical autonomic neuropathy in leprosy patients has been reported, and autonomic nerve dysfunction may be an early manifestation of the disease. Autonomic dysfunction features in leprosy include anhidrosis, impaired sweating function, localised alopecia ,and reduced heart rate variability. Urinary retention and intestinal pseudo-obstruction have been described in Lyme disease. Diphtheritic polyneuropathy, tetanus and botulism are examples of bacterial infections releasing toxins that affect the autonomic nervous system. Autonomic dysfunction may be responsible for additional morbidity in some infectious diseases.

Salmonellosis is one of the major causes of food poisoning in Japan. In general, consumption of food contaminated with non-typhi Salmonella causes acute gastroenterocolitis. However, salmonellosis has also been reported to be associated with development of severe extraintestinal multiorgan complications, including rhabdomyolysis (RM), acute renal failure (ARF), and rarely acute encephalopathy [1–5]. In this paper, we report on a patient with systemic lupus erythematosus (SLE) who developed ARF with suspected acute encephalopathy following Salmonella enteritidis infection. The patient was under treatment with immunosuppressive agents. Since patients with SLE are at an increased risk of severe infections [6], this case report may serve to emphasize the importance of prevention of food poisoning and of advocating appropriate hygienic practice in immunocompromised hosts. A 16-year-old Japanese girl with a 3-year history of SLE with WHO class IV disease was referred to our hospital because of drowsiness and disorientation. Although the SLE activity and serum complement levels were reasonably controlled under maintenance therapy with prednisolone (15 mg/day) and azathioprine (75 mg/day), the patient developed acute severe diarrhea, vomiting, and fever after eating a raw egg. She was admitted to a regional hospital with suspected food poisoning. On admission, her body weight was 36.5 kg, which represented a loss of about 1.5 kg over her previous weight recording. Her blood pressure was decreased to 70/36 mmHg. Laboratory studies revealed the following: peripheral white blood cell (WBC) count 11,200/μl, hemoglobin 13.8 g/dl, hematocrit 39.9%, platelet count 193,000/μl, blood urea nitrogen (BUN) 18.2 mg/dl, creatinine 0.9 mg/dl, and Creactive protein (CRP) 5.4 mg/dl. Despite adequate fluid replacement, the patient developed oliguria, drowsiness, and disorientation. Lumbar puncture revealed clear cerebrospinal fluid (CSF), and further examination of the CSF revealed the following: cell count 1 cell/mm, protein 22 mg/dl, glucose 71 mg/dl, and sterile culture. Emergency cranial computed tomographic and electroencephalographic findings were unremarkable. The BUN and serum creatinine increased to 41.5 mg/dl and 4.7 mg/dl, respectively. In addition, the serum level of creatinine kinase (CK) and urinary level of myoglobin also became markedly elevated to 21,307 IU/l (normal: 12–144 IU/l) and 1,073 ng/ml (normal: 0–70 ng/ml), respectively. A diagnosis of ARF caused by RM associated with some central nervous system (CNS) complication was made, and the patient was transferred to our hospital. Physical examination on admission to our hospital revealed that the patient was drowsy. Her blood pressure was 126/76 mmHg. Laboratory studies revealed the following: WBC count 10,590/μl, hemoglobin 13.9 g/100 ml, hematocrit 38.0%, platelet count 119,000/μl, serum total protein 6.6 g/dl, albumin 3.9 g/dl, BUN 63 mg/dl, creatinine 6.8 mg/dl, sodium 137 mmol/l, potassium 4.3 mmol/l, chloride 97 mmol/l, calcium 6.8 mg/dl, CRP 17.8 mg/dl, and CK 29,484 IU/l. Immunological studies revealed the following: IgG 502 mg/dl, IgA 185 mg/dl, IgM 43 mg/dl, C3 76 mg/dl (normal: 79–152 mg/dl), C4 20 mg/dl (normal: 16–38 mg/dl), and complement hemolytic activity 37.4 U/ml (normal: 23–46 U/ml). The serological test for antinuclear antibody was positive at a titer of 1:320, with a homogeneous pattern. Although the blood culture was negative, the stool culture was positive for Salmonella enteritidis. A search for endotoxin in the blood was negative. The levels of the proinflammatory cytokines, interleukin (IL)-6 and IL-8, were analyzed in the CSF specimen obtained at the onset of the salmonellosis. The CSF levels of both cytokines were significantly elevated: IL-6 328 pg/ml (measured by enzyme immunosorbent assay, normal: less than 4.0 pg/ml) and IL-8 327 pg/ml (measured by enzyme-linked immunosorbent assay, normal: less than 2.0 pg/ml). On the T. Nakahata . K. Tsugawa . H. Tanaka (*) Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan e-mail: hirotana@cc.hirosaki-u.ac.jp

Guillain–Barre syndrome (GBS) is an acute onset, usually monophasic immune-mediated disorder of the peripheral nervous system. The term GBS is often considered to be synonymous with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but with the increasing recognition of variants over the past few decades, the number of diseases that fall under the rubric GBS have grown to include axonal variants and more restricted variants, such as Miller Fisher syndrome (MFS) [Table 1].[1] Table 1 Guillain–Barre syndrome—clinical variants Epidemiology The reported incidence rates for GBS are 1–2 per 100,000 population.[2–4] The lifetime likelihood of any individual acquiring GBS is 1:1000.[5] The subtypes of GBS have different incidence rates in different parts of the world. In Europe and North America AIDP is dominant contributing to 90% of the cases. In contrast in China and Japan AMAN being the most common subtype.[6,7] The picture is intermediate when we look at other population. In Indian series the incidence of AIDP and AMAN are virtually equal although AMAN is more common in younger patients.[8] There seems to be a slight preponderance of AIDP in studies by Gupta et al[9] and by Meena et al (unpublished data from NIMS, Hyderabad). Available Indian literature indicates a peak incidence between June–July and Sept–October.[10] In western countries, GBS is common in the 5th decade,[11] but in India it occurs more commonly at a younger age.[10,12] GBS is equally common in men and women and can occur at any age. There is a male preponderance among the hospitalized population.[10,12]

Codeine-Induced Sensory Neuropathy, Autonomic Dysfunction, and Myopathy.

A Case of Cerebral Venous Thrombosis in a 77-Year-Old White Man

Background: Guillain-Barré syndrome (GBS) is a peripheral nervous system inflammatory disease that is the most prevalent cause of acute flaccid paralysis, with an annual global incidence of 1-2 per 100,000 person-years. GBS typically appears with acute ascending flaccid paralysis and sensory abnormalities in anesthetic glove stockings; paralysis may extend to cranial muscles. Although the disease’s clinical presentation is diverse and there are multiple discrete clinical forms, myelopathy as a sign of GBS is a relatively unusual condition. Case presentation: GBS is diagnosed in a 29-year-old woman with myelopathy symptoms such as tetraparesis, hypoesthesia below the level of second thoracal myelum, aberrant proprioceptive in lower extremities, retention of urine and anhidrosis. We perform a lumbar puncture, and a cerebrospinal fluid (CSF) examination reveals albumin-cytological dissociation. Cervico-thoracic magnetic resonance imaging (MRI) revealed no abnormalities. Demyelinating polyradiculopathy was discovered using electromyography (EMG) and nerve conduction studies (NCS). Discussion: The classical presentation of GBS is progressive (ascending) limb weakness with decreased or absent physiological reflexes. Pharyngeal–cervical–brachial variation and face diplegia with paraesthesia are rare variations of GBS. Our patient presented with ascending limb weakness accompanied by a disturbance in the central nervous system but had similiar serological biomarker, which may be another rare variant of GBS. Conclusion: Diagnosis of GBS is quite challenging. GBS has a wide range of clinical symptoms. EMG-NCV and lumbar puncture are still required in myelopathic individuals with normal MRI, and unusual GBS symptoms should be explored. As a result, the choice of therapy and management becomes more appropriate.

Background Enteroviruses (EVs) can cause infections and outbreaks of mild to severe diseases, such as central nervous system (CNS) and systemic infections. The contribution of EVs to acute CNS/systemic infections requiring hospitalization was assessed by analysing data extracted from virology laboratory database. Methods Real-life data obtained from two molecular virology laboratories located in Northern Italy were retrieved from databases and analysed retrospectively. The queries used to extract the data were (i) requests for EV-RNA detection in clear cerebrospinal fluid (CSF) specimens collected from hospitalized patients with suspected acute CNS (including aseptic meningitis, encephalitis, and acute flaccid myelitis/paralysis) or systemic infections (sepsis-like illness or fever (≥ 38°C) of unknown origin), (ii) CSF samples collected from January 1st, 2015, to December 31st, 2017. Results 582 requests of EV-RNA detection in CSF samples collected from as many patients of any age were recorded. EV-RNA was detected in 4.5% of the CSF samples; 92.3% of EV-positive cases were patients < 15 years, 58.3% of whom were < 3 months. EVs circulated all-year-round, and the highest EV-positive rates were observed from May to August. The risk of EV infection and the relative illness ratio value among children < 1 − year − old were significantly higher than those observed for older patients. Conclusions EV surveillance should be carried out for all pediatric patients < 15 years and especially children less than 1 year of age with clinically suspected CNS infection/systemic infections. The implementation of a laboratory-based surveillance established for analysing the virological data provided by laboratories that routinely perform EV molecular testing may enable us to determine the impact of EVs that can cause infections requiring hospitalization.

ABSTRACTObjectives Cerebral vasospasm after subarachnoid haemorrhage (SAH) is associated with cerebrovascular contractile receptor upregulation resulted from haemolysis in the subarachnoid space. This study developed a new magnesium-rich artificial cerebrospinal fluid (MACSF) formula and investigated its effects on receptor-mediated contraction in rat basilar arteries.Methods Clear and haemorrhagic cerebrospinal fluid (CSF) were collected from patients with hydrocephalus or SAH. MACSF was freshly prepared using clinical intravenous injections. Rat basilar arteries were segmented and incubated with clear CSF, haemorrhagic CSF or MACSF. The contractile responses were studied by myograph. The messenger ribonucleic acid (mRNA) and protein expression of 5-hydroxytryptamine 1B (5-HT1B), endothelin subtype B (ETB) and endothelin subtype A (ETA) receptors were evaluated by real-time polymerase chain reaction (PCR) and Western blot analyses.Results Haemorrhagic CSF exposure shifted the contractile curves induced by 5-hydroxytryptamine (5-HT), sarafotoxins 6c (S6c) and endothelin-1 (ET-1) leftward with increased maximal contraction values. Furthermore, mRNA and protein expression were markedly elevated for 5-HT1B, ETB and ETA receptors on arteries exposed to haemorrhagic CSF. However, the contractile responses to 5-HT, S6c or ET-1 and expression of 5-HT1B, ETB and ETA receptors in rat cerebral arteries exposed to MACSF remained unaffected compared to those exposed to clear CSF. Besides, unlike normal saline which can inactive in-vitro vessels, MACSF can maintain their physiological activity.Conclusion Haemorrhagic CSF induces upregulation of 5-HT1B, ETB and ETA receptors in rat cerebral arteries. However, MACSF can maintain in-vitro rat basilar arteries in good physiological activity and normal expression of contractile 5-HT and ET receptors.

Near infrared spectrophotometric (NIRS) algorithms to determine the tissue oxygen saturation (TOI) assume a semi-infinite, homogenous tissue geometry. At the head, the clear cerebrospinal fluid (CSF) layer may violate this assumption. The aim was to estimate the error in the TOI values caused by the CSF layer in vitro and to confirm the results in vivo. The liquid phantom mimicking the neonatal head, consisted of a spherical shell of silicone filled with a liquid solution (1% Intralipid, 60 mumol/l haemoglobin, yeast) and a clear layer imitating CSF. The solution was oxygenated and deoxygenated, while measuring its TOI and pO2. Without clear layer the mean TOI was 90.9 +/- 0.5% at pO2 > 18 kPa and decreased to 26.0 +/- 1.3% at pO2 = 0 kPa. With a clear layer the TOI increased from 27.8 +/- 0.8% at pO2 > 18 kPa to 68.0 +/- 0.8% at pO2 = 0 kPa. The clear layer caused a large error in the TOI. In ten mechanically ventilated infants (postnatal age 0.03 to 8 months) the TOI (at the head) and arterial oxygen saturation (SaO2) were measured while the inspired oxygen fraction was altered. The TOI was always positively correlated with the SaO2 (mean slope linear regression = 0.89, r2 = 0.62). Thus an adverse effect of the CSF layer on TOI measurements can be excluded for infants. The CSF layer is not modelled correctly in the phantom.

Penicillin-resistant Neisseria meningitidis and Pandemic 2009 H1N1 Influenza Coinfection in a Child

Introduction: The physical examination of the cerebrospinal fluid (CSF) is part of its routine evaluation and is easily performed as soon as CSF is obtained. However, its predictive value of CSF abnormalities is poorly known. Objective: In this study we evaluated the predictive value for CSF abnormalities leukocytes count among clear and colorless CSF in cases of suspected central nervous system (CNS) infection. Methods: We retrospectively evaluated data from CSF samples collected from suspected CNS infection that were classified as clear and colorless. This visual categorization was performed by the collector physician and by biomedical staff experienced in CSF analysis. The CSF cell count were considered normal when CSF white blood cells were up to 3 cells/mm3 , protein was below 45 mg/dL, glucose above 50 mg/dL, and lactate bellow 19.6 mg/ dL. The proportion of normal CSF and normal CSF parameters were recorded. Results: 34,434 CSF samples from suspected CNS infection were included. Of those, 22,960 were classified as clear and colorless (66.7%). Among clear and colorless CSF samples 13,137 (57.2%) had normal CSF cytology and biochemical findings. The probability of CSF abnormalities in the cytological and/ or biochemical examination in clear and colorless CSF samples obtained from patients with suspected CNS infection was 42.8%. Discussion: In this study, we showed a high frequency of cytological and/or biochemical abnormalities in clear and colorless CSF obtained from patients with suspected CNS infection. Conclusions: Viral infections and other inflammatory CNS diseases are among the conditions that may present with clear and colorless CSF. Therefore, a clear and colorless CSF in suspected CNS infections has a little predictive value for CSF abnormalities.