Ritu Shree

The Diagnostic Dilemma of Neurolymphomatosis.

Neurolymphomatosis (NL) defined as infiltration of the central nervous system or the peripheral nervous system (PNS) by malignant lymphoma cells is a rare clinical entity. However, the increasing use of fluorodeoxyglucose positron-emission tomography (FDG-PET) and magnetic resonance imaging in evaluating PNS disorders is resulting in; this condition being recognized more frequently. Here; we report five NL patients and review the current literature. We report five patients with non-Hodgkins lymphoma (NHL) and NL, all of whom were men aged 47–69 years. The clinical presentation varied from symmetrical peripheral neuropathy to mononeuropathy. Peripheral neuropathy was the presenting manifestation of a systemic lymphoma in two patients (40%). Neuroimaging as well as whole-body FDG-PET helped in determining the correct diagnosis in all of the patients. NL is an unusual presentation of NHL resulting from infiltration of the PNS by malignant lymphomatous cells. While evaluating peripheral neuropathy, a high degree of suspicion of NL is required since the presenting symptoms vary, conventional radiology has only modest sensitivity, and a pathological diagnosis is often difficult. FDG-PET helps in the early diagnosis and treatment of this condition.

Clinical and radiological predictors of outcome in tubercular meningitis: A prospective study of 209 patients

OBJECTIVES The predictors of poor outcome in tuberculous meningitis (TBM) remain to be delineated. We determined role of various clinical, radiological and cerebrospinal fluid (CSF) parameters in prediction of outcome in TBM. PATIENTS AND METHODS Current study was a prospective observational study including 209 patients of TBM. All patients underwent detailed evaluation including Gadolinium enhanced Magnetic resonance imaging (GdMRI) of brain as well as tests to detect evidence of tuberculosis elsewhere in body. They also underwent GdMRI at three and nine month follow up. All patients received treatment as per standard guidelines. RESULTS Mean age was 30.4±13.8years. 139 (66.5%) patients had definite TBM while 70 (34.5%) had highly probable TBM. 53 (25.4%) patients died. On univariate analysis, longer duration of illness, altered sensorium, stage III TBM, hydrocephalus and exudates correlated with poor outcome. On multivariate analysis presence of hydrocephalus (p=0.003; OR=3.2; 95% CI=1.5-6.7) and stage III TBM (p<0.0001; OR=8.7; 95% CI=3.7-20.2) correlated with higher risk of mortality. In addition, there was significant positive association between presence of hydrocephalus (p=0.05; OR=2.2; 95% CI=0.97-5.1), stage III TBM (p<0.0001; OR=28; 95% CI=4.9-158) and presence of altered sensorium (p=0.05; OR=22; 95% CI=0.99-4.8) with either death or survival with severe disability. CONCLUSIONS It is possible to prognosticate TBM using a combination of clinical and radiological. The duration of illness (65.9±92days) before diagnosis of TBM continues to be unacceptably long and this stresses on need to educate primary care physicians about TBM. Future studies where intensity and duration of treatment is guided by these cues may help in sorting out some of the most difficult questions in TBM, namely duration of antitubercular therapy as well as dose and duration of steroid therapy etc.

Tuberculomas in “Critical” Locations of the Visual Pathway—A Masquerader

ABSTRACT Tuberculosis never stops fascinating physicians. The burden of tuberculosis is a major cause of disability. While drugs are often blamed when patients develop new focal deficits on treatment, the deterioration in these patients can have a myriad of causes including the development of new tuberculomas. Recognizing the critically located tuberculomas as potential causes of vision loss is indispensable. Here, we report two patients with strategic tuberculomas leading to vision loss. In one patient, the cause of visual morbidity was compression of the optic pathways; in the other patient, cortical vision loss was noted due to strategic location of tuberculomas.

Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India

BACKGROUND Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. AIM AND OBJECTIVES To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. PATIENTS AND METHODS Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n=146) and CSF (n=140) levels of various proinflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers (n=99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. RESULTS Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1β, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1β with severity of hydrocephalus; c) High CSF IL1β and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1β with presence of infarcts on MRI brain. CONCLUSION Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Feeding Dystonia: Feeding Dystonia

A 45-year-old female with no prior comorbidities presented with a history of generalized tonic-clonic seizures, trouble while chewing and swallowing food, spontaneous tongue protrusion, and lip bites of three years duration. Examination revealed oro-lingual dystonia, classically present during eating, resulting in throwing out of food bolus, dysarthria, bilateral upper limb chorea, and generalized areflexia (Video 1, segment 1). Her brother had a similar presentation with oro-lingual dystonia while eating (Video 1, segment 2), generalized areflexia, and seizures for two years. There was no history of exposure to neuroleptic drugs.

Hypothalamic and pituitary dysfunction is common in tubercular meningitis: A prospective study from a tertiary care center in Northern India

INTRODUCTION Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.

Pearls & Oy-sters: An unusual cause of hypokalemic paralysis

A 47-year-old woman presented with history of recurrent episodes of transient quadriparesis associated with documented hypokalemia for the last 12 years (serum K+ levels documented during those episodes were 1.7–3.2). She was diagnosed with HP at another center and was on supplemental potassium for the last 6 years. She also complained of transient, postprandial, binocular blurring of vision, progressing to persistent progressive painless vision loss bilaterally for the last 2 months. There was a history of dry mouth and eyes. There were no other systemic or neurologic complaints. General examination results were normal. Visual acuity was reduced to perception of light in the left eye and 6/60 in the right eye. There was bilateral optic atrophy and left-sided relative afferent pupillary defect. The rest of the neurologic and general physical examination was normal. MRI revealed hyperintense signal changes in bilateral optic nerves, optic chiasma, and optic tracts with mild contrast enhancement. Serum anti-aquaporin 4 antibodies were negative. CSF analysis was normal (no cells, normal glucose [86 mg/dL], and normal protein [42 mg/dL]). Investigations revealed metabolic acidosis (arterial pH 7.24), persistent hypokalemia (serum potassium 2.9 mEq/L [normal range 3.5–5.5]), hyperchloremia (serum chloride 122 mEq/L vs normal upper limit of 108 mEq/L), low serum bicarbonate (9 mEq/L [normal range 23–26 mEq/L]), and high urinary pH (6) without aminoaciduria or glycosuria (table). Renal, thyroid, and liver function tests and serum calcium, magnesium, and phosphorus were normal. The overall picture was that of hyperchloremic metabolic acidosis with normal anion gap, suggestive of distal renal tubular acidosis (RTA). Antinuclear antibody (ANA) was strongly positive; anti-Ro and anti-La titers were highly raised (24,952 U/mL and 12,713 U/mL, respectively, vs normal upper limits of 10 U/mL). Schirmer test revealed markedly reduced lacrimation (0 mm bilaterally). Ninety-nine meter TcO4 scintigraphy revealed negligible tracer uptake in both parotid and submandibular glands. Nerve conduction studies revealed autonomic neuropathy (absent sympathetic skin response) and ultrasonography of kidneys revealed simple cortical cysts. Final diagnosis of SS with distal RTA and hypokalemic paralysis, optic nerve involvement, and autonomic neuropathy was made and the patient was started on 60 mg prednisolone daily with oral potassium supplements. She improved initially in visual acuity, but developed acute right ophthalmoplegia with nasal obstruction (onset to peak 2 days) after 3 weeks of treatment. Repeat MRI of brain revealed findings suggestive of invasive rhino-orbitocerebral fungal infection. Nasal biopsy revealed invasive mucormycosis. She received IV amphotericin B but died of her illness after 2 weeks. A whole-body autopsy was done that confirmed invasive rhinocerebral mucormycosis along with pulmonary and hepatic dissemination along with evidence of SS in the form of tracheobronchial submucosal layer lymphocytic infiltration (figure, A) and medullary and papillary nephrocalcinosis (figure, B and C).