Hardeep Singh Malhotra

Paradoxical reaction in HIV negative tuberculous meningitis

This review focusses on paradoxical reactions occurring during the treatment of tuberculous meningitis (TBM) in human immunodeficiency virus-negative cases. A paradoxical reaction is defined as the worsening of a pre-existing lesion or the appearance of new lesion in a patient whose clinical symptoms initially improved with anti-tuberculosis treatment. A number of different paradoxical reactions have been reported in patients with TBM including expansion of existing cerebral tuberculomas, and appearance of new tuberculomas, hydrocephalus, and optochiasmatic and spinal arachnoiditis. While the exact mechanism of paradoxical reactions is uncertain, an exaggerated immune reaction against Mycobacterium tuberculosis-associated antigens is currently the most accepted theory for tuberculous paradoxical reaction. Corticosteroids are considered to have a beneficial effect in the management of paradoxical reactions. Immuno-modulatory drugs, including tumor necrosis factor-α antagonists, thalidomide and interferon-γ have been used in isolated cases with more severe forms of paradoxical reactions.

Neuroimaging Features and Predictors of Outcome in Eclamptic Encephalopathy: A Prospective Observational Study

Imaging findings in 45 patients with eclampticposterior reversible encephalopathy syndrome were assessed. The most common affected areas were the occipital, parietal, frontal, and temporal lobes. Serum creatinine, uric acid, and lactate dehydrogenase values and presence of moderate or severe PRES were significantly associated with mortality. Eclamptic PRES demonstrated a higher incidence of atypical distributions and cytotoxic edema than previously thought. BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is associated with eclampsia. We assessed the distribution and nature of typical and atypical cranial MR imaging findings in these patients and their correlation with clinical and laboratory data and predictors of outcome. MATERIALS AND METHODS: Forty-five clinically confirmed cases of eclampsia were included in this prospective observational study. Subjects with hemolysis, elevated liver enzymes, and low platelets syndrome (n = 9) and pre-existing neurologic conditions (1 with cerebral solitary cysticercus granuloma) were excluded. Patients underwent blood investigations and cranial MR imaging. RESULTS: Twenty-seven patients had abnormal while 8 had normal MR imaging findings. Involvement of brain regions was as follows: frontal, 88.89%; temporal, 44.44%; parietal, 100%; occipital, 100%; deep gray matter, 29.63%; cerebellum, 22.22%; brain stem, 14.81%. Cytotoxic edema was present in 33.33% of cases; 66.67% of patients had mild posterior reversible encephalopathy syndrome; 25.92% had moderate posterior reversible encephalopathy syndrome; and 7.41% had severe posterior reversible encephalopathy syndrome. Abnormal neuroimaging findings were significantly associated with altered sensorium; visual disturbances; status epilepticus; and elevated serum creatinine, uric acid, and lactate dehydrogenase (P = .006, P = .018, P = .015, P = .019, P = .003, and P = .001, respectively). Serum creatinine, uric acid, and lactate dehydrogenase values and the presence of moderate or severe posterior reversible encephalopathy syndrome were significantly associated with mortality (P < .001, P < .001, P = .009, and P = .027, respectively). CONCLUSIONS: Neuroimaging in eclampsia demonstrates a higher incidence of atypical distributions and cytotoxic edema than previously thought. Altered sensorium; visual disturbances; status epilepticus; and elevated serum uric acid, lactate dehydrogenase, and creatinine are associated with abnormal neuroimaging findings. Higher serum creatinine, uric acid, and lactate dehydrogenase levels and moderate and severe forms of posterior reversible encephalopathy syndrome are possible predictors of poor outcome.

Neurologic complications in dengue virus infection A prospective cohort study

Objective: This study aimed to evaluate the incidence and clinical spectrum of neurologic complications, predictors of central and peripheral nervous system involvement, and their outcome in patients with dengue virus infection (DENV). Methods: To determine the extent of neurologic complications, we used a hospital-based prospective cohort study design, which included laboratory-confirmed cases of dengue and follow-up for 3 months. We also analyzed clinical and laboratory data to assess predictors of neurologic involvement. Results: The study included enrollment of 486 cases. Two were lost to follow-up and excluded. Forty-five patients developed neurologic complications. Of these, 28 patients had CNS and 17 had peripheral nervous system (PNS) involvement, representing an incidence rate for neurologic complications of 9.26%. Significant predictors of CNS involvement were higher mean body temperature (p = 0.012), elevated hematocrit (p = 0.009), low platelet count (p = 0.021), and liver dysfunction (p < 0.001). Predictors of PNS involvement were higher mean body temperature (p = 0.031), rash (p = 0.002), and elevated hematocrit (p < 0.001). The mortality rate was 4.5%. The remainder of the patients recovered. Conclusion: An increasingly wide spectrum and higher incidence of neurologic complications of DENV are reported. Clinical and laboratory parameters such as higher mean body temperature, rash, increases in hematocrit, thrombocytopenia, and liver dysfunction are independent predictors of neurologic complications.

Clinico-radiological predictors of vascular cognitive impairment (VCI) in patients with stroke: A prospective observational study

BACKGROUND AND PURPOSE Cognitive dysfunction occurs commonly following stroke and varies in severity. This study was aimed to determine the clinical, neuro-imaging, laboratory predictors of post stroke cognitive impairment and factors related to poor functional outcome in patients with post-stroke vascular cognitive impairment (VCI). MATERIAL AND METHODS We prospectively evaluated 102 of 240 consecutive stroke patients for 6 months after incident stroke for development of VCI. Patients with VCI comprised of those with VCI-no dementia (VCIND) and vascular dementia (VaD). Functional outcome was assessed by modified Barthel index (MBI). RESULTS Frequency of post-stroke VCI was 45.1% (46/102): 26.5% (27/102) having VCI-ND and 18.6% (19/102) having VaD. Patients with VCI were more likely to have lower educational and socioeconomic status, diabetes, hypertension, prior stroke, multiple risk factors, urinary incontinence, gait abnormality, peripheral signs of atherosclerosis, higher blood sugar level on admission and LDL levels, strategic site lesion, higher ARWMC (age related white matter changes) score, worse stroke severity (NIHSS) and functional outcome scores. On logistic regression analysis, lower educational status, strategic site lesion, higher ARWMC score and baseline stroke severity score were found to independently predict the risk of developing VCI. Worse stroke severity (NIHSS) scores and functional status scores at baseline predicted poor outcome in patients with VCI. CONCLUSION Post-stroke cognitive impairment is frequent and is associated with poor functional outcome. Predictors like lower educational status, strategic site lesion, greater severity of age related white matter changes and baseline stroke severity independently contributed to the risk of developing VCI in stroke patients.

Boomerang sign: Clinical significance of transient lesion in splenium of corpus callosum.

Transient signal abnormality in the splenium of corpus callosum on magnetic resonance imaging (MRI) is occasionally encountered in clinical practice. It has been reported in various clinical conditions apart from patients with epilepsy. We describe 4 patients with different etiologies presenting with signal changes in the splenium of corpus callosum. They were diagnosed as having progressive myoclonic epilepsy (case 1), localization-related epilepsy (case 2), hemicrania continua (case 3), and postinfectious parkinsonism (case 4). While three patients had complete involvement of the splenium on diffusion-weighted image (“boomerang sign”), the patient having hemicrania continua showed semilunar involvement (“mini-boomerang”) on T2-weighted and FLAIR image. All the cases had noncontiguous involvement of the splenium. We herein, discuss these cases with transient splenial involvement and stress that such patients do not need aggressive diagnostic and therapeutic interventions. An attempt has been made to review the literature regarding the pathophysiology, etiology, and outcome of such lesions.

Dengue-associated neuromuscular complications

Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evolving course; benign nature; excellent response to potassium; and, often leads to diagnostic confusion with other dengue-associated neuromuscular disorders. Rhabdomyolysis is the most severe form of muscle involvement and may be life-threatening. Guillain-Barrι syndrome is another frequent neuromuscular dengue-associated complication. Dengue-associated Guillain-Barrι syndrome responds very well to intravenous immunoglobulins. Predominant spinal gray matter involvement has been reported in a patient presenting with areflexic paraparesis. Mononeuropathies often manifest with paralysis of the diaphragm due to phrenic nerve dysfunction. Brachial plexopathy, in the form of neuralgic amyotrophy, has been described much more frequently than lumbo-sacral plexopathy. Early recognition of these neuromuscular complications is needed for successful treatment and to prevent further disabilities.

Etiological spectrum of hypokalemic paralysis: A retrospective analysis of 29 patients

Background: Hypokalemic paralysis is characterized by episodes of acute muscle weakness associated with hypokalemia. In this study, we evaluated the possible etiological factors in patients of hypokalemic paralysis. Materials and Methods: We reviewed the records of 29 patients who were admitted with a diagnosis of hypokalemic paralysis. Modified Guillain-Barre´ Syndrome disability scale was used to grade the disability. Results: In this study, 15 (51.7%) patients had secondary causes of hypokalemic paralysis and 14 patients (42.3%) had idiopathic hypokalemic paralysis. Thyrotoxicosis was present in six patients (20.6%), dengue infection in four patients (13.7%), distal renal tubular acidosis in three patients (10.3%), Gitelman syndrome in one patient (3.4%), and Conns syndrome in one patient (3.4%). Preceding history of fever and rapid recovery was seen in dengue infection-induced hypokalemic paralysis. Approximately 62% patients had elevated serum creatinine phosphokinase. All patients had recovered completely following potassium supplementation. Patients with secondary causes were older in age, had significantly more disability, lower serum potassium levels, and took longer time to recover. Conclusion: In conclusion, more than half of patients had secondary causes responsible for hypokalemic paralysis. Dengue virus infection was the second leading cause of hypokalemic paralysis, after thyrotoxicosis. Presence of severe disability, severe hypokalemia, and a late disease onset suggested secondary hypokalemic paralysis.

Tuberculous optochiasmatic arachnoiditis: a devastating form of tuberculous meningitis

Tuberculous meningitis is primarily a disease of the meninges of brain and spinal cord along with adjacent brain parenchyma. The characteristic pathological changes are meningeal inflammation, basal exudates, vasculitis and hydrocephalus. Tuberculous meningitis has a strong predilection for basal parts of the brain. Exudates, if dominantly present in the interpeduncular, suprasellar and Sylvian cisterns, result in optochiasmatic arachnoiditis and tuberculoma. Optochiasmatic arachnoiditis and tuberculoma are devastating forms of tuberculous meningitis and often associated with profound vision loss. This clinical entity more frequently affects young adults. In a recent study, on the multivariate logistic regression analysis, female sex, younger age and raised cerebrospinal fluid protein content were identified as predictors for developing optochiasmatic arachnoiditis. Frequently, optochiasmatic tuberculoma and optochiasmatic arachnoiditis develop paradoxically while a patient is being treated with anti-TB drugs. MRI reveals confluent enhancing lesions that are present in the interpeduncular fossa, pontine cistern, and the perimesencephalic and suprasellar cisterns. Management of tuberculous optochiasmatic arachnoiditis and optochiasmatic arachnoiditis tuberculoma has been variable. Treatment of optochiasmatic arachnoiditis continues to be a challenge and the response is generally unsatisfactory. In isolated case reports and in small series, corticosteroids, methyl prednisolone, thalidomide and hyaluronidase have been used with variable success. The benefit from neurosurgery is controversial and deterioration may follow the initial temporary improvement. Management of paradoxical optochiasmatic arachnoiditis is also controversial. Some patients regain vision following treatment with anti-TB drugs and continued usage of corticosteroids. Neurosurgery may be considered in the patients with either treatment failure or when diagnosis is in doubt. In conclusion, presence of optochiasmatic arachnoiditis or tuberculoma has important therapeutic and prognostic implications for patients of tuberculous meningitis.

Seizure recurrence in patients with solitary cystic granuloma or single parenchymal cerebral calcification: A comparative evaluation

BACKGROUND Solitary cysticercus granuloma and single parenchymal calcified lesion are two common neuroimaging abnormalities in Indian patients with epilepsy. In this study, we evaluated the frequency and predictors of seizure recurrence in patients presenting with new onset epilepsy or single epileptic seizures and these two different imaging findings. MATERIALS AND METHODS We enrolled 115 patients with newly diagnosed epilepsy. All patients were clinically evaluated and were treated with oxcarbazepine. No anti-helminthic treatment was prescribed. The patients were followed up for 6 months. In the solitary cystic granuloma group, repeat computed tomography was done after 6 months. RESULTS The study included 80 patients with solitary cysticercus granuloma and 35 patients with a single calcified lesion. Twenty (25%) patients with solitary cysticercus granuloma and 12 (34.3%) patients with parenchymal calcified lesion had a seizure recurrence during the study period (p = 0.307). After 6 months, 57 (71.3%) patients in the solitary cysticercus granuloma group demonstrated complete resolution of the granuloma and in 21 (26.2%) patients the granuloma transformed into a calcified lesion. In the solitary cysticercus granuloma group, a family history of seizure, serial seizures and calcification on follow-up neuroimaging (p < 0.05) were significantly associated with recurrence of seizures. In patients with a single parenchymal calcified lesions, electroencephalographic abnormalities and serial seizures (p = < 0.05) were significant predictors of recurrence. Kaplan-Meier statistics revealed that the seizure recurrence rate was insignificantly higher in patients with calcified lesions than in patients with solitary cysticercosis granulomas. CONCLUSION In conclusion, in patients with solitary cysticercus granuloma, a family history of seizures, serial seizures and calcification of the granuloma, and in patients with a calcified brain lesion, electroencephalographic abnormalities, family history of epilepsy and serial seizures were associated with an increased risk of seizure recurrence.

Solitary cysticercus granuloma

Solitary cysticercus granuloma is considered the most frequent type of neurocysticercosis in India and many other southeast Asian countries. It has frequently been reported from developed countries in immigrant populations. Genetic susceptibility has recently been linked with Toll-like receptor gene polymorphisms. These lesions are the most frequent neuroimaging abnormality seen in patients with new-onset epilepsy. Solitary cysticercus granuloma is seen on a contrast computed tomography as an enhancing ring-shaped lesion. These enhancing lesions are usually less than 20 mm in diameter and are surrounded by a varying amount of perilesional vasogenic edema. A variety of infectious, neoplastic, inflammatory or vascular diseases can manifest with a single ring-enhancing lesion of the brain, and differential diagnosis may be challenging. The most difficult differential diagnosis is small intracranial tuberculoma. Immunodiagnosis is often not helpful in the patients with single lesions. Antiepileptic treatment is the most important option. Albendazole and corticosteroids are of questionable value. Prognosis is generally good. Antiepileptic therapy can be withdrawn after disappearance of the lesion. Calcification of the lesion and perilesional gliosis may be responsible for frequent seizure recurrences.