Tuberculous infection of skeletal muscle in a case of dermatomyositis

A patient with dermatomyositis associated with carcinoma was treated with steroids and antibiotics for possible tuberculosis. Autopsy showed an overwhelming diffuse nongranulomatous infection of Mycobacterium tuberculosis involving only the skeletal muscles and one inguinal lymph node. The rare localization of tuberculosis to skeletal muscle in this case is possibly due to steroid immunosuppression and the humoral immune attack on muscle blood vessels that is a part of dermatomyositis. © 1994 John Wiley & Sons, Inc.     

Intrathecal Baclofen Pump Infection With Meningitis: Effective Treatment by Radical Debridement and Intrareservoir Baclofen–Vancomycin Co-Infusion

ObjectivesIntrathecal baclofen pump associated central nervous system (CNS) infection and meningitis is a rare but serious complication and may have dire consequences. Due to bacterial biofilm formation, the optimal treatment strategy is usually for removal of the pump, followed by systemic antibiotics for treatment of local and CNS infection. We describe this case of a patient with recurrent Staphylococcus aureus pump site empyema and meningitis leading to status dystonicus, who was successfully managed with radical debridement and intrareservoir baclofen–vancomycin co-infusion.Materials and MethodsWe retrospectively report a case of infected intrathecal baclofen pump with meningitis and provide a full review of literature.ConclusionsTo the best of our knowledge, this is the first reported case of intrathecal baclofen (ITB)-associated pump site empyema and meningitis successfully treated with this technique. In selected cases where surgical explantation is deemed not feasible, this method can provide clinicians with an additional option for pump salvage and retention, while eradicating CNS infection and maintaining optimal control of spasticity and dystonia.     

The immune response to Mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis

Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune diseases. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.     

Intracerebral Mycobacterium bovis bacilli Calmette–Guerin infection-induced immune responses in the CNS

To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette–Guerin. Granuloma and IFN-γ⁺CD4⁺ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4⁺ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4⁺ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3⁺CD4⁺ T cells and PD-L2⁺ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection.     

Aspergillus arachnoiditis post intrathecal baclofen pump insertion

This report describes an unusual fungal infection of an intrathecal baclofen pump which, to our knowledge, has not been reported previously. We describe a 39-year-old man with severe lower limb spasticity due to secondary progressive multiple sclerosis that was managed with insertion of an intrathecal baclofen pump. He subsequently presented with distinct neurological decline secondary to an intrathecal baclofen pump infection with Aspergillus terreus.     

Continuous Intrathecal Baclofen Infusion by a Programmable Pump in 131 Consecutive Patients with Severe Spasticity of Spinal Origin

We began this study to determine the efficacy and safety of intrathecal baclofen (ITB) delivered by a programmable pump for the treatment of severe spasticity of spinal cord origin. One hundred fifty two patients with severe spasticity of spinal origin, refractory to oral baclofen, or who experienced intolerable side‐effects were given a test dose of ITB. Only those who had a satisfactory response were considered to be appropriate for pump implantation. All but one of the 152 patients had a satisfactory response, and the pump was implanted in 131 patients. Pre‐ and postoperative spasticity scores were compared and analyzed. The mean Ashworth score for rigidity decreased from 4.2 preoperatively to 1.3 (p < 0.0005) on ITB. The spasm score decreased from a mean of 3.4 to 0.6 (p < 0.0005). Reduction of spasticity resulted in improved levels of physical activity, decreased pain, and augmentation of sleep. Drug‐related complications included constipation, muscular hypotonia, urinary retention, erectile dysfunction, nausea, dizziness, drowsiness, hypotension and bradycardia as well as tolerance to baclofen. Some patients experienced post‐spinal puncture headaches. Catheter‐related problems included occlusions, breaks, punctures, and dislodgments. Superficial pump pocket infection, pocket erosion, cerebrospinal fluid (CSF) leak, post‐spinal puncture headache, and meningitis were some of the procedure‐related complications. Two pumps flipped and another pump valve was stuck. We conclude that long‐term intrathecal baclofen by an implanted programmable pump is a safe and effective method of treating severe intractable spinal spasticity.     

Muscle phenotype in patients with myotonic dystrophy type 1

Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand‐held dynamometry. Myotonia was evaluated by a handgrip test and by analyzing the decrement of the compound muscle action potential. Muscle biopsies were assessed for morphological changes and Na⁺‐K⁺ pump content. Results: Muscle strength correlated with a decline in Na⁺‐K⁺ pump content (r = 0.60, P < 0.001) and with CTG expansion. CTG expansion did not correlate with severity of myotonia, proximal histopathological changes, or Na⁺‐K⁺ pump content. Histopathologically, we found few centrally placed nuclei (range 0.2–6.9%). Conclusions: The main findings of this study are that muscle weakness correlated inversely with CTG expansion and that central nuclei are not a prominent feature of proximal muscles in DM1. Muscle Nerve 47:409‐415, 2013     

A comparision of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients

Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebro-spinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods. Received: 8 November 1995 Received in revised form: 9 July 1996 Accepted: 19 July 1996     

Calcitonin pump improves nerve regeneration after transection injury and repair

Introduction: After nerve injury, excessive calcium impedes nerve regeneration. We previously showed that calcitonin improved nerve regeneration in crush injury. We aimed to validate the direct effect of calcitonin on transected and repaired nerve. Methods: Two rat groups (n = 8) underwent sciatic nerve transection followed by direct repair. In the calcitonin group, a calcitonin‐filled mini‐osmotic pump was implanted subcutaneously, with a catheter parallel to the repaired nerve. The control group underwent repair only, without a pump. Evaluation and comparison between the groups included: (1) compound muscle action potential recording of the extensor digitorum longus (EDL) muscle; (2) tetanic muscle force test of EDL; (3) nerve calcium concentration; and (4) nerve fiber count and calcified spot count. Results: The calcitonin pump group showed superior recovery. Conclusions: Calcitonin affects injured and repaired peripheral nerve directly. The calcitonin‐filled mini‐osmotic pump improved nerve functional recovery by accelerating calcium absorption from the repaired nerve. This finding has potential clinical applications. Muscle Nerve 51 : 229–234, 2015     

Primary granulomatous angiitis of the CNS preferentially involving small veins with a granulomatous leukoencephalitis‐like lesion in the cerebrum

We have reported an autopsy case of primary granulomatous angiitis of the CNS preferentially involving the small veins with a granulomatous leukoencepalitis‐like lesion in the cerebral white matter of a 48‐year‐old man. The latter lesion was ischemic necrosis due to circumferential multiple perivenous granulomas in the adjacent Virchow‐Robin space. Multifocal progressive involvement of venular adventitia by granulomas, leaving behind mural fibrosis and luminal stenosis, was related clinically to the prolonged stepwise deterioration observed in the patient, and pathologically to diffuse loosening with dilated veins in the deep cerebral white matter and subcortical hemorrhagic infarction in the left parietal lobe through chronic venous stagnation. PCR demonstrated negativity for Mycobacterium tuberculosis and Propionibacterium acnes, and in situ hybridization with EBV‐encoded small nuclear RNA probe was also negative. The possibility of subarachnoidal latent infection with an unknown avirulent agent causing exclusively perivascular granulomas is proposed. It will be necessary to examine by autopsy whether the type (artery or vein) and size of the involved vessels and the pathological subtype of angiitis is related to the etiopathogenesis and prognosis. It is also pointed out that the entity of lymphocytic angiitis is problematic.     

Astrocyte‐mediated infantile‐onset leukoencephalopathy mouse model

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile‐onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte‐specific Mlc1 overexpression causes infantile‐onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na⁺/K⁺ ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na⁺/K⁺ pump. In contrast, no changes in Na⁺/K⁺ pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na⁺/K⁺ pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile‐onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile‐onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150–168     

Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis

We have noted two morphologically distinct types of atypical lymphocytes (AL) in the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we designate type-I AL, with multilobulated nuclei resembling those of the abnormal cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by large lymphocytes with basophilic cytoplasm and nuclei containing coarse chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other viruses, but not in meningitis resulting from Cryptococcus neoformans (n = 14), Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15), or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in meningitis of various aetiologies and in aseptic meningeal reactions, but not in leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to be indicative of enteroviral meningitis with the highest predictive value (69%), while type-II AL had a lower diagnostic positive predictive value in meningitis of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL were stained for CD8. The presence of type-I AL in CSF strongly suggests enteroviral meningitis, which warrants careful follow-up without antifungal, antituberculous or antibacterial agents. However, type-I AL, which are likely to be virally transformed lymphocytes, must be distinguished from ATL cells, which frequently involve the meninges. Received: 29 May 1997 Received in revised: 1 November 1997 Accepted: 20 March 1998     

Intrathecal Baclofen for the Treatment of Intractable Spasticity of Spine or Brain Etiology

Objective. To determine the long‐term relief of spasticity and complication rates in patients who underwent placement of a programmable intrathecal baclofen pump for treatment of medically intractable spasticity of spine or brain etiology. Methods. Sixty‐two consecutive adult patients who underwent placement of a programmable pump were retrospectively reviewed. Results. Spasticity was clinically and statistically significantly decreased in all patients. Catheter‐related kinks, breaks, dislodgments, and disconnections were the most common complications followed by drug‐related effects, infections, and wound complications. Conclusions. Intrathecal baclofen is a very effective strategy for the relief of medically intractable spasticity of spine or brain etiology. Even though 36% of patients have required revisions, no patient has experienced any long‐term morbidity. Patients and their primary care givers have been pleased with the long‐term effects of this therapy upon quality of life.     

Continuous antibiotic prophylaxis and cerebral spinal fluid infection in patients with intracranial pressure monitors

Introduction: Inconsistencies in the recommendation of prophylactic antibiotics for patients with intracranial pressure monitors compelled us to assess the effect of our standard regimen of continuous antibiotic prophylaxis on cerebrospinal fluid infection. We examined the rate, possible risk factors, causative organisms, and characteristics of infection. Methods: Three hundred eleven patients admitted between September 1998 and February 2001 with an intracranial pressure monitoring device in place were included. Two hundred eleven patients received a ventriculostomy, 95 an intraparenchymal fiber optic intracranial pressure monitor (ICPM), and 5 both an ICPM and a ventriculostomy. Results: The overall infection rate was 5.5% (17/311). No patient with an ICPM developed CSF infection. The infection rate among ventriculostomy patients was 8.1% (17/211). The majority of infections (82%) were caused by Gram-positive species. Younger age (OR=1.04 for each year, 95% CI=1.01–1.08, p=0.03) and increasing duration of ventriculostomy insertion (OR=1.2 for each day of catheter insertion, 95% CI=1.1–1.3, p<0.001) were risk factors for CSF infection in multivariate analysis. Infected patients experienced longer lengths of stay in the NICU (p<0.001) and hospital (p<0.001); however, infection did not impact clinical outcome, as measured by mortality and discharge GCS. Conclusion: ICP monitors have a low overall infection rate. When infection occurs, gram positive organisms predominate. For patients with ventriculostomy, duration of catheter insertion strongly predicts infection, but did not alter in-hospital mortality.     

Selective dorsal rhizotomy as an alternative to intrathecal baclofen pump replacement in GMFCS grades 4 and 5 children

Background

Conventionally, selective dorsal rhizotomy (SDR) has been reserved for ambulant children and implantation of intrathecal baclofen (ITB) pump for non-ambulant children with cerebral palsy. Rather than replacing the ITB pump in selected Gross Motor Function Classification System (GMFCS) grades 4 and 5 children, we elected to undertake SDR instead. We discuss the rationale and outcomes.

Objectives

To assess if children with severe spasticity treated with long-term ITB pump would benefit from SDR as alternative procedure to replacement of ITB pump.

Method

This study is a prospective review of ten children with severe spasticity. Indications for ITB pump replacement in 3/10 children were previous ITB pump infection and the remaining seven were nearing depletion of drug delivery system. Pre- and post-SDR mean modified Ashworth scores, assessment of urological function and survey of parent/carer satisfaction were undertaken.

Result

Mean Ashworth score reductions post-SDR in the lower limbs and upper limbs were 2.4 and 1.70, respectively. An improvement in urological function was also noticed in 27 % of patients. Overall, 90 % of parents/carers felt that functional outcome with SDR was improved compared with that of ITB.

Conclusion

SDR in comparison to ITB in this subgroup is cheaper, less intrusive by avoiding refills/replacement and found to be more effective than ITB in reducing spasticity and providing ease for nursing care. We therefore suggest that consideration should be given to SDR as an alternative in patients previously implanted with ITB systems complicated by infection or nearing end of battery life.

     

Meningitis associated with bilateral optic papillitis following Mycoplasma pneumoniae infection

Mycoplasma pneumoniae (M. pneumoniae) is a frequent cause for human infection, and central nervous system disease associated with M. pneumoniae infection is being reported with increasing frequency. We described herein a 60-year-old woman who developed meningitis associated with bilateral optic papillitis following M. pneumoniae infection and discussed the possible mechanisms. To our knowledge, there have been only a few reports that described the meningitis complicated by bilateral optic papillitis in association with M. pneumoniae infection. Our case highlighted the protean neurological manifestations of M. pneumoniae infection.     

Tuberculous meningitis with hydrocephalus Contribution of PCR assay of CSF before VP shunting

A 10-month-old infant with tuberculous (Tb) meningitis accompanying hydrocephalus was successfully treated with a VP shunt operation soon after a PCR assay of CSF was found to be negative for Mycobacterium tuberculosis. PCR assay of CSF is helpful for determination of the timing for VP shunting in Tb meningitis. Received: 15 March 1996 Revised: 9 January 1998     

Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner

Na⁺/K⁺ ATPase is a plasma membrane-localized sodium pump that maintains the ion gradients between the extracellular and intracellular environments, which in turn controls the cellular resting membrane potential. Recent evidence suggests that the pump is also localized at synapses and regulates synaptic efficacy. However, its precise function at the synapse is unknown. Here we show that two mutations in the α subunit of the eat-6 Na⁺/K⁺ ATPase in Caenorhabditis elegans dramatically increase the sensitivity to acetylcholine (Ach) agonists and alter the localization of nicotinic Ach receptors at the neuromuscular junction (NMJ). These defects can be rescued by mutated EAT-6 proteins which lack its pump activity, suggesting the presence of a novel function for Ach signaling. The Na⁺/K⁺ ATPase accumulates at postsynaptic sites and appears to surround Ach receptors to maintain rigid clusters at the NMJ. Our findings suggest a pump activity-independent, allele-specific role for Na⁺/K⁺ ATPase on postsynaptic organization and synaptic efficacy.     

Induction of infarct tolerance by platelet-derived growth factor against temporary focal ischemia

Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague–Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 μg in total), 7 days (2 μg or 4 μg in total), or 14 days (4 μg in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 μg in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 μg in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.     

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study

Abstract Gastric emptying (GE) may be driven by tonic contraction of the stomach (‘pressure pump’) or antral contraction waves (ACW) (‘peristaltic pump’). The mechanism underlying GE was studied by contrasting the effects of clonidine (α₂‐adrenergic agonist) and sumatriptan (5‐HT₁ agonist) on gastric function. Magnetic resonance imaging provided non‐invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min^?1 IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r² = 49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r² = 15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the ‘pressure pump’ mechanism.