BACKGROUND

Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT) images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM) to SPECT.

METHODS

After linear spatial normalization of brain perfusion SPECT using 99mTc-ethyl cysteinate dimer (99mTc-ECD) to a Talairach space, high-dimension-warping was done using an original 99mTc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2) between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C) patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images.

RESULTS

SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99mTc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution.

CONCLUSIONS

The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT.

We present two female siblings with familial juvenile nephronophthisis (FJN) which was diagnosed at the early stage of renal failure. Diagnosis was made during the investigation of anemia in case 1 and by a subsequent family survey in case 2. Most patients with FJN are not identified until the terminal stage of renal failure and such cases have rarely been reported in Japan. Case 2 had a reduction in the maximum urinary concentration ability but no azotemia, and among the FJN patients reported in Japan so far she has the least advanced renal disease. Histological examination of the renal biopsy in case 1 showed typical findings of FJN, such as thickening and lamination of the tubular basement membrane (TBM), interstitial fibrosis, and round cell infiltration of the interstitium. In case 2, renal biopsy revealed an irregular marked thickening of the TBM with trivial interstitial changes and a normal glomerular appearance. The histology of these two cases suggests that the TBM may be the primary site affected in FJN.

OBJECTIVE

The role of Ommaya reservoir implantation in children with tuberculous meningitis hydrocephalus (TBMH) has been seldomly reported. Therefore, we performed this study to determine the role of the Ommaya reservoir in the treatment of children with TBMH.

METHODS

We retrospectively analyzed the effects of Ommaya reservoir implantation in 12 children with TBMH. Intracapsular puncture of the reservoir was performed for draining the cerebrospinal fluid and the TBM was treated by intraventricular injection of isoniazid.

RESULTS

The ideal treatment outcome was observed in nine (75 %) of the 12 children; two (16.7 %) children developed serious disabilities and one of them (8.3 %) eventually died. The treatment method was effective for all six (100 %) children with Palur grade II TBM but showed no effect in three (50 %) children with grade III and IV TBM. The number of leukocytes in the cerebrospinal fluid decreased to 20 × 10(6)/L (75 %) within 2 weeks after implantation of the reservoirs. Finally, the Ommaya reservoirs in eight children were removed but were retained in four children. Four children had to undergo ventriculoperitoneal shunt.

CONCLUSIONS

Ommaya reservoir implantation has been shown to be effective in treating children with TBMH. This method may be largely suitable for children with early grade II TBM or partly in children with grade III TBM who have mild or moderate hydrocephalus that can alleviate after short-term treatment. Thus, a good proportion of children who undergo Ommaya reservoir implantation can avoid ventriculoperitoneal shunt surgery.

Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P<0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.

BACKGROUND

Childhood tuberculosis is a major public health problem in developing countries with tubercular meningitis being a serious complication with high mortality and morbidity.

OBJECTIVE

To study the clinicopathological as well as radiological profile of childhood tuberculous meningitis (TBM) cases.

METHODS

Prospective, observational study including children <14 years of age with TBM admitted in a tertiary care hospital from Western India.

METHODS

TBM was diagnosed based on predefined criteria. Glassgow coma scale (GCS) and intracranial pressure (ICP) was recorded. Staging was done as per British Medical Council Staging System. Mantoux test, chest X-ray, cerebrospinal fluid (CSF) examination, neuroimaging, and other investigations were done to confirm TB.

METHODS

STATA software (version 9.0) was used for data analysis. Various risk factors were determined using Chi-square tests, and a P< 0.05 was considered significant.

RESULTS

Forty-seven children were included, of which 11 (24.3%) died. Fever was the most common presenting symptom, and meningismus was the most common sign. Twenty-nine (62%) children presented with Stage III disease. Stage III disease, low GCS, and raised ICP were predictors of mortality. Findings on neuroimaging or CSF examination did not predict mortality.

CONCLUSIONS

Childhood TBM presents with nonspecific clinical features. Stage III disease, low GCS, lack of Bacillus Calmette-Guérin vaccination at birth and raised ICP seem to the most important adverse prognostic factors.

1. In cyclophosphamide-induced cystitis in the rat, cholinergic function of the bladder and muscarinic receptor expression are altered. In the present study, we investigated whether the toad urothelial cell line TBM-54 expresses functional muscarinic receptors and whether changes in muscarinic receptors can be induced in vitro by treating cells with acrolein, a metabolite of cyclophosphamide causing cystitis. 2. The occurrence of muscarinic receptors on cells was assessed by microphysiometry, a method analysing receptor function by measuring changes in the extracellular acidity rate (ECAR) in response to receptor stimulation. 3. Challenging untreated cells with the muscarinic receptor agonist carbachol gave rise to a concentration-dependent increase in changes in ECAR, with a maximal response at 1 mmol/L carbachol of 51 +/- 6%. Pre-incubating cells with different muscarinic receptor antagonists (i.e. pirenzepine (M(1) receptor selective), methoctramine (M(2)/M(4) receptor selective) and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP; M(3)/M(1)/M(5) receptor selective)), gave rise to a concentration-dependent decrease in the effects of carbachol (0.5 mmol/L) on changes in ECAR. 4. Western blot analysis was used to determine the expression of all muscarinic receptor subtypes (M(1)-M(5)) by the cell line. Following acrolein treatment, cells were markedly less sensitive to carbachol and the expression of muscarinic M(2) receptors was decreased, whereas the expression of muscarinic M(3) receptors was increased. 5. In conclusion, the urothelial cell line TBM-54 expresses functional muscarinic receptors and exposure to acrolein leads to a modulation in the expression of muscarinic receptors. Consequently, acrolein may have direct effects on muscarinic receptor function and expression that contribute to the pathogenesis of cyclophosphamide-induced cystitis.

We have examined the mineralocorticoid specificity in a TBM 18-23 cell line derived from the toad bladder epithelium. In cells grown on porous substrate, corticosterone was more potent than aldosterone in stimulating a sodium transport response, measured by the short-circuit current method 6 h after hormone addition [mean affinity constant (K0.5) for corticosterone = 1 nM vs. K0.5 for aldosterone = 8 nM]. The time course of effects and saturation kinetics were identical for both agonists, suggesting interaction with identical receptors. Whereas the dose-response relationship for aldosterone did not change with time of incubation (6 vs. 24 h), the dose-response curve for corticosterone became biphasic at 24-h incubation (apparent K0.5 as high as 40 nM), demonstrating that corticosterone became apparently less potent with time. Pretreatment with carbenoxolone, a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), restored full sensitivity at 24-h incubation to corticosterone. The 11 beta-HSD activity was low during the first 3 h of incubation in the presence of 3 nM corticosterone, and only a small fraction (approximately 7%) of corticosterone was metabolized. At 24-h incubation, 11 beta-HSD activity increased approximately 2.5-fold (P < 0.001, n = 8). We conclude that 11 beta-HSD activity is induced by its own substrate in TBM cells in parallel with the induction of the carbenoxolone-sensitive sodium transport response.

Objective It is difficult to make the differential diagnosis between tuberculous meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The objective of this study was to create a diagnostic rule for differentiating TBM from CM in adult HIV-negative patients based on clinical and laboratory features. Methods The clinical and laboratory data of 219 adult HIV-negative patients satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University during the period 2000-2009 were retrospectively analyzed. Features found to be independently predictive of tuberculous meningitis were modeled using a multivariate logistic regression to create a diagnostic rule. The performance of the diagnostic rule was assessed using a prospective test data method. Results Six factors were found to be predictive of a diagnosis of tuberculous meningitis: gender, mental disorders, vision and/or hearing damage, proteins in the cerebrospinal fluid, the total cerebrospinal fluid white cell count and the coexistence of tuberculosis in peripheral organs. The diagnostic rule developed using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9% positive predictive value and 84.4% negative predictive value. The corresponding values for the diagnostic rule were 70.0% and 88.0% using prospective test data. Conclusion Clinical and laboratory features can be helpful in the differential diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV-negative patients.

Tuberculous meningitis (TBM) is a devastating infection of the central nervous system lacking an adequate point-of-care diagnostic test. We conducted a prospective cohort study of 550 Zambian adults with suspected TBM to determine the diagnostic accuracy of cerebrospinal fluid (CSF) Xpert MTB/RIF, CSF lipoarabinomannan (LAM), urine LAM, CSF total protein, and CSF glucose compared with the gold standard of CSF culture. We categorized patients with a positive CSF tuberculosis (TB) culture as definite TBM. We also assessed inpatient and 1-year mortality on definite TBM patients when CSF Xpert MTB/RIF results were available in real time to treating physicians relative to a historical comparison cohort in whom Xpert results were not available in real time. Of the 550 patients, 474 (86.2%) were HIV-infected and 105/550 (19.1%) had definite TBM based on a positive CSF culture. The sensitivity/specificity of the diagnostic tests were CSF Xpert MTB/RIF, 52.9%/94.2%; CSF LAM, 21.9%/94.2%; urine LAM, 24.1%/76.1%; and CSF glucose <40 mg/dl, and total protein, >100 mg/dl, 66.3%/90%. A model including CSF Xpert MTB/RIF, CSF LAM, CSF glucose, and CSF total protein demonstrated an area under the receiver operating curve of 0.90. The inpatient and 1-year mortality for definite TBM was 43% and 57%, respectively. There was low sensitivity for the diagnosis of TBM across all diagnostics tests. CSF Xpert MTB/RIF and CSF LAM are highly specific for the diagnosis of TBM. Despite the use of Xpert MTB/RIF for diagnostic purpose in real time, TBM was still associated with a high mortality in Zambian patients.

METHODS

Tuberculous meningitis (TBM) is a severe complication of tuberculosis (TB) predominantly affecting young children. Early initiation of treatment is important to prevent morbidity and mortality associated with TBM, emphasising the importance of early diagnosis. Among the most promising new methods for diagnosing TB are antigen-detection assays based on the detection of lipoarabinomannan (LAM).

OBJECTIVE

To evaluate the diagnostic value of a commercial, antigen-capture enzyme-linked immunosorbent assay (ELISA) test based on the detection of LAM in urine for the early diagnosis of TBM in children.

METHODS

A cross-sectional study in which urine samples from paediatric patients with suspected TBM attending the Tygerberg Children's Hospital, Cape Town, South Africa, were tested for LAM.

RESULTS

Complete data were available for 50 of 56 patients with suspected TBM. TBM was diagnosed in 21 (42%) patients and excluded in 29 (58%). The LAM ELISA had a sensitivity of 4.8% and a specificity of 93.1%. Serial measurements in the first 2 weeks after treatment initiation did not improve test performance.

CONCLUSIONS

We have shown that urinary LAM detection was of little value for the diagnosis of TBM in a cohort of paediatric patients with suspected TBM.

BACKGROUND

Revised National Tuberculosis Control Programme (RNTCP) of Government of India provides intermittent thrice-a-week directly observed treatment short course (RNTCP regimen).

OBJECTIVE

Assessments of all-cause mortality and nine-month morbidity outcomes of patients with tuberculous meningitis (TBM) on RNTCP regimen.

METHODS

We prospectively followed up patients registered with RNTCP center, with a diagnosis of TBM from January 1(st), 2010 to December 31(st), 2011. Morbidity was assessed using modified Rankin Scale (mRS).

RESULTS

We had 43 patients with median duration for follow-up of 396 days and that of survivors of 425 days. Two patients defaulted. Fourteen patients (32.5%) had mRS score of 4 to 6 and 29 had mRS of 0 to 3 after 9-month treatment. Severe disability was not related to any factor on logistic regression. Severe disability was seen in one patient (6.66%) among the 15 patients with stage 1, nine (37.5%) out of 24 patients with stage 2 and three (75%) out of 4 patients with stage 3 disease. Eight patients died (18.6%) of whom 4 died during the intensive phase and 4 during the continuation phase of RNTCP regimen. Mortality was independently related to treatment failure with adjusted Hazard ratio of 8.29 (CI: 1.38-49.78) (P = 0.02). One patient (6.66%) died out of the 15 patients with stage 1 disease, 5 (20.8%) out of 24 patients with stage 2 disease and 2 (50%) out of the 4 with stage 3 disease.

CONCLUSIONS

RNTCP regimen was associated with good compliance, comparable mortality and morbidity.

OBJECTIVE

DNA amplification by the polymerase chain reaction (PCR) was evaluated as a means for rapid diagnosis of tuberculous meningitis (TBM).

METHODS

A 240 bp region (nts 460-700) from the MPB 64 protein coding gene specific for Mycobacterium tuberculosis (TB) was selected for amplification. Nineteen clinical samples were studied. Six were obtained from patients with TBM diagnosed by culture (4/6) or by response to therapy (2/6). The remaining 13 samples were obtained from patients with febrile seizu es (8/13), aseptic meningitis (3/13) and septic meningitis (2/13), and these served as negative controls.

RESULTS

We detected TB DNA in all the 6 CSF specimens obtained from patients with TBM. PCR alone was sufficient to detect TB DNA in 5 of these 6 samples. However, one sample was positive only when PCR was followed by oligonucleotide hybridisation. In the 2 patients whose CSF were obtained only after commencement of TB therapy, TB cultures were negative but positive on PCR nd oligoprobe labelling. The diagnosis of TBM was confirmed based on their remarkable response to therapy. Twelve of the thirteen negative controls were TB DNA negative. There was one false positive sample, which was thought to be due to TB DNA contamination.

CONCLUSIONS

Taken together, our results indicate that DNA amplification using PCR, followed by oligonucleotide hybridisation offers a rapid (5 working days) means of diagnosis of TBM, provided care is taken to ensure that cross contamination of DNA samples is avoided.

The present study describes the development and evaluation of a duplex polymerase chain reaction (D-PCR) for diagnosis and simultaneous identification of tuberculous meningitis (TBM) and bacterial meningitis (BM) in a single reaction. A D-PCR with primers amplifying portions of the Mycobacterium tuberculosis IS6110 and the eubacteria 16SrDNA sequence in a same reaction mix was developed and tested on DNA extracted from 150 clinical CSF samples from different categories (TBM = 39, BM = 26, control infectious and non-infectious category = 85). The results indicate a clear differentiation between bands for eubacteria and M. tuberculosis with an analytical sensitivity of 10(3) cfu/ml for eubacteria and 10(2) cfu/ml for M. tuberculosis. When evaluated in clinical samples, D-PCR overall diagnosed 100 % confirmed TBM and 100 % confirmed BM cases with overall specificity of 96.5 %. D-PCR can be an effective tool for diagnosis and simultaneous identification of TBM or BM in a single PCR reaction. It saves time, cost, labour and sample amount and help in administration of appropriate antimicrobial therapy. The proposed diagnostic assay would be helpful in correct and rapid management of TBM and BM patients.

Polymerase chain reaction (PCR) based on the amplification of a 169 bp DNA fragment specific for the Mycobacterium tuberculosis complex was evaluated for the rapid diagnosis of tuberculous meningitis (TBM). A total of 105 CSF specimens from clinically suspected cases of TBM were studied. Clinical details of the cases and cytochemical parameters of the CSF specimens were recorded. For PCR 10 CSF specimens from cases other than TBM, 4 non-mycobacterial culture isolates (one strain of E coli, one strain of proteus species and 2 strains of salmonella species) and one sample of sterile distilled water were processed as negative controls. For positive control standard culture of Mycobacterium tuberculosis H37Rv was processed with every batch of specimens. Besides PCR, smear for AFB by the Ziehl-Neelsen (ZN) and the fluorochrome method and culture on Lowenstein-Jensen medium was also carried out. By PCR, 31.42% specimens were found positive, whereas by conventional culture on Lowenstein-Jensen medium only 3.8% specimens were positive.

Bacteriological confirmation of tuberculous meningitis (TBM) is problematic, and rarely guides initial clinical management. A uniform TBM case definition has been proposed for research purposes.

We prospectively enrolled patients aged 3 months to 13 years with meningitis confirmed using cerebrospinal fluid analysis at Tygerberg Hospital, Cape Town, South Africa. Criteria that differentiated TBM from other causes were explored and the accuracy of a probable TBM score assessed by comparing bacteriologically confirmed cases to 'non-TBM' controls.

Of 139 meningitis patients, 79 were diagnosed with TBM (35 bacteriologically confirmed), 10 with bacterial meningitis and 50 with viral meningitis. Among those with bacteriologically confirmed TBM, 15 were Mycobacterium tuberculosis culture-positive and 20 were culture-negative but positive on GenoType(®) MTBDRplus or Xpert(®) MTB/RIF; 18 were positive on only a single commercial nucleic acid amplification test. A probable TBM score provided a sensitivity of 74% (95%CI 57-88) and a specificity of 97% (95%CI 86-99) compared to bacteriologically confirmed TBM.

A probable TBM score demonstrated excellent specificity compared to bacteriological confirmation. However, 26% of children with TBM would be missed due to the limited accuracy of the case definition. Further prospective testing of an algorithm-based approach to TBM is advisable before recommendation for general clinical practice.

BACKGROUND

Tuberculous peritonitis (TBP) is a well-known complication of ventriculo-peritoneal (VP) shunt treatment for hydrocephalus resulting from tuberculous meningitis (TBM). However, a case of hydrocephalus unrelated to TBM resulting from VP shunt malfunction due to TBP has not been reported.

METHODS

A 21-year-old male presented with nausea, abdominal pain, and headache. VP and cysto-peritoneal (CP) shunts had been inserted to treat hydrocephalus due to a suprasellar arachnoid cyst, replaced the VP and removed the CP in his childhood. Computed tomography demonstrated acute hydrocephalus and an abdominal pseudocyst surrounding the distal end of the peritoneal tube. Initial laboratory data showed elevated white blood cell count and C-reactive protein level, but no causative pathogen was identified. External drainage of cerebrospinal fluid (CSF) and of the fluid in the peritoneal cyst was established, and empirical antibiotic therapy was initiated. Bacterial cultures eventually revealed Mycobacterium tuberculosis infection, and TBP was diagnosed. The patient responded well to antituberculosis (anti-TB) agents and insertion of a ventriculo-pleural shunt.

CONCLUSIONS

This case highlights the possibility of CSF shunt failure and concomitant neurological sequelae from TB infection even when the pathogen has not invaded the central nervous system, as in TBM. Moreover, TBP is rare in developed countries and therefore may be misdiagnosed because of nonspecific clinical features and low sensitivity of common TB screening methods.

OBJECTIVE

Clinicians often perform follow-up lumbar punctures (LPs) on patients with tuberculous meningitis (TBM) to document changes occurring in the cerebrospinal fluid (CSF). Normalisation of the CSF then serves as indirect confirmation of the diagnosis. However, changes occurring in CSF following the initiation of anti-tuberculosis (TB) treatment are not well described. We undertook a retrospective study to determine the temporal evolution of CSF in patients with TBM on anti-TB treatment in an attempt to provide a more rational basis for the interpretation of repeat LPs.

METHODS

Patients diagnosed with TBM at King George V Hospital in Durban from 1994 to 2003 were identified. Demographic, clinical, laboratory and radiological data were recorded. We examined the change in CSF lymphocyte cell count, polymorphonuclear (PMN) cell count, glucose concentration and protein concentration. Initially, scatter plots of the data modelled over time were produced and random effects models were then used to model the predicted changes in CSF over time.

RESULTS

Ninety-nine patients were identified, and a total of 327 LPs were done. The average number of LPs per patient was 3 (range 3 - 9). Statistically significant changes in all four variables (lymphocytes, PMN cells, glucose and protein) were demonstrated, with a p value < 0.001. The predicted models showed that lymphocyte count and protein concentration change slowly over time. PMN cells and glucose concentration changed rapidly in an exponential manner.

CONCLUSIONS

Our results demonstrate the tendency for CSF to normalise over time. The slow change in lymphocyte count and protein concentration limits clinical use. The rapid change in PMN cells and glucose concentration allows us to make reasonable clinical decisions. If a repeat LP does not show definite improvement in these two parameters, it should be considered atypical for TBM.

Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is one of the severest forms of tuberculosis. At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional "gold standard" based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect Mycobacterium tuberculosis (M.Tb) bacilli in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional "gold standard", the various molecular-based methods, such as polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of TBM. Moreover, nested PCR assay has been reported as a key method that drastically increases the sensitivity and specificity of DNA amplification compared with conventional single-step PCR. Currently, a novel assay technique, which is internally controlled and combines the high sensitivity of nested PCR with the accurate quantification of real-time PCR, namely, Wide Range Quantitative Nested Real-time PCR (WR-QNRT-PCR) assay, has been developed. This novel assay technique is useful for the rapid diagnosis and the assessment of anti-tuberculosis treatment during clinical course of TBM. Therefore, in actual clinical practice, its wider use for diagnosis of TBM is expected in the future.

One-hundred-and-thirty-six children below 12 years of age hospitalized with a diagnosis of tuberculous meningitis (TBM) have been investigated to identify the underlying cause of convulsions. One-hundred-and-one children (74 per cent) presented with seizures before and/or during hospitalization. Generalized tonic and clonic seizures (GTCS) were the commonest (58 per cent) type of seizures followed by focal seizures (FS) (38 per cent) and tonic spasms (TS) (4 per cent). EEG changes were more frequently observed in cases with FS and in those children with GTCS who presented after first week of hospitalization. EEG findings included generalized dysrythmia with paroxysmal slow activity (38 per cent), interhemispheric asymmetry (23 per cent), multiple spike and wave pattern (10 per cent), and focal spike and wave pattern (15 per cent). CT scan findings were more common in those children with GTCS and TS who presented with recurrent seizures and/or seizures manifesting after first week of hospitalization. FS presenting at any stage of the disease were associated with CT scan abnormalities. Abnormalities detected in CT scan of brain included meningeal enhancement (55 per cent), hydrocephalus (32 per cent), tuberculomas (27 per cent), and cerebral infarctions (13 per cent). Clinical presentation and investigations indicate that the probable cause of convulsions could be attributed to cerebral edema (57 per cent), syndrome of inappropriate secretion of antidiuretic hormone (35 per cent), hydrocephalus (32 per cent), tuberculoma (27 per cent), abnormal electric focus (25 per cent), and cerebral infarction (13 per cent).

To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u.>> 0.5 g/day, group IV had serum creatine level (Cr)>> 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.

BACKGROUND

Patients with tuberculous meningitis (TBM) have been frequently observed to have excessive sleep during the day and frequent awakenings during night. We undertook this study to evaluate sleep related abnormalities in patients with TBM since there is no published literature pertaining to the same.

OBJECTIVE

To study sleep wake cycles in patients with tuberculous meningitis by actigraphy and sleep logs and compare these with age and sex matched controls.

METHODS

Consecutive patients admitted with tuberculous meningitis were studied clinically and with three days of continuous wrist actigraphy and sleep/wake parameters were compared to those of age and gender matched normal healthy controls.

RESULTS

Forty three patients with tuberculous meningitis were enrolled in the study. Of these, twenty-eight patients (15 females, 13 males; mean age 31.64 years) who were able to complete adequate actigraphy were compared with an equal number of controls (15 females, 13 males; mean age 30.93 years). Patients were found to have greater sleep time (p<0.0005) and more sleep episodes (p<0.0005) during the day while during the night they had less sleep (p<0.0005) with more frequent (p=0.019) and longer (p<0.0005) awakenings as compared to normal controls. Majority of the patients had reversal of sleep/wake cycles. There was poor co-relation between sleep parameters measured by actigraphy and sleep logs.

CONCLUSIONS

Tuberculous meningitis is associated with significant alteration of sleep-wake circadian cycles. This needs to be further characterized through studies involving polysomnography. There is a need to address these specific sleep difficulties to improve the quality of life of the patient as well as the care-giver.

Primary productivity of terrestrial vegetation is expected to increase under the influence of increasing atmospheric carbon dioxide concentrations ([CO2]). Depending on the fate of such additionally fixed carbon, this could lead to an increase in terrestrial carbon storage, and thus a net terrestrial sink of atmospheric carbon. Such a mechanism is generally believed to be the primary global driver behind the observed large net uptake of anthropogenic CO2 emissions by the biosphere. Mechanisms driving CO2 uptake in the Terrestrial Biosphere Models (TBMs) used to attribute and project terrestrial carbon sinks, including that from increased [CO2], remain in large parts unchanged since those models were conceived two decades ago. However, there exists a large body of new data and understanding providing an opportunity to update these models, and directing towards important topics for further research. In this review we highlight recent developments in understanding of the effects of elevated [CO2] on photosynthesis, and in particular on the fate of additionally fixed carbon within the plant with its implications for carbon turnover rates, on the regulation of photosynthesis in response to environmental limitations on in-plant carbon sinks, and on emergent ecosystem responses. We recommend possible avenues for model improvement and identify requirements for better data on core processes relevant to the understanding and modelling of the effect of increasing [CO2] on the global terrestrial carbon sink.

Cerebral ischaemia is a serious complication of tuberculous meningitis (TBM) with the anterior circulation most commonly affected. Acute syringomyelia is a very rare complication of TBM. Here, we report an unusual presentation of TBM with a third nerve palsy as a result of posterior circulation stroke as well as a syringomyelia.

It has been shown in experimental models that cell-mediated immunologic mechanisms can lead to glomerular as well as tubulointerstitial renal injury, with or without concomitant antibody-mediated effects. The glomerular lesions are characterized by varying combinations of monocyte and, to a lesser extent, lymphocyte influx, necrosis, and proliferation of intrinsic glomerular cells. The tubulointerstitial lesions have generally been characterized by interstitial infiltrates containing numerous T lymphocytes and, often, numerous macrophages, sometimes with invasion of tubules and tubular cell damage. Although similar renal abnormalities are seen in several human renal diseases, further evidence is obviously required to establish a pathogenetic role for cellular immunity. Analyses of infiltrating mononuclear cells by immunohistochemical methods, with monoclonal antibodies that identify subsets of T cells, have indirectly supported a role for delayed hypersensitivity reactions in tubulointerstitial nephritis resulting from drugs or associated with anti-TBM antibodies, as well as a role for both delayed hypersensitivity and cytolytic lymphocyte effects in renal allografts. However, only with the development of methods that permit the identification of subsets of lymphocytes with unique functions, as well as the identification of the antigen specificity of the cells, will it be possible to understand fully the renal lesions that are now suspected of being cell-mediated.