Anubhav Thukral

Slurred speech and spirochaetes

In July, 2008, a 20-year-old man presented to our outpatient department complaining of fever, headache, vomiting, and altered behaviour. 12 days earlier, he had developed the high grade intermittent fever, of up to 40·0°C. It appeared daily, subsided with antipyretics, and had no diurnal variation. He later developed headache and vomiting, along with agitated behavior and slurred speech. He had previously been well; in particular, there was no history of seizures, any focal neurological defi cit, and no history of bleeding from any part of the body. On examination our patient was pale with prominent bilateral subconjunctival haemorrhages (fi gure); his vital signs were stable. He was conscious and oriented to time, place, and person, but was irritable. Neck rigidity was present. His speech was slurred. There were signs of cerebellar involvement in the form of past-pointing, positive fi nger-nose test, and ataxia. Other systemic examinations were normal. Travel history from a family member revealed that the young man had been to his grandfather’s house in a village 20 days earlier, where he had worked barefoot in the paddy fi elds (rice farm) for a few days. Blood tests showed anaemia (113 g/L), deranged coagulation profi le (platelets 95×109 per L; INR 1·33; and APTT 45 s), and high serum concentrations of alkaline phosphatase (587 IU/L), aspartate aminotransferase (203 IU/L), and alanine aminotransferase (133 IU/L) MRI of the brain was within normal limits. CSF analysis showed mild pleiocytosis with normal glucose and protein con centrations; this, along with the history of travel, prompted us to investigate for leptospirosis. Serology for IgM antibody to leptospira was positive. Tests for malarial parasite were negative. We started our patient on ampicillin and he became afebrile 2 days later, and his cerebellar ataxia improved after 10 days. Leptospirosis is a zoonotic disease caused by the spirochaete, Leptospira interrogans. Clinical manifestations can range from asymptomatic infection to the lifethreatening Weil’s syndrome. It is transmitted to people usually through contact with water contaminated by urine from rodents (commonly rats). After an incubation period of 7–10 days, the leptospiraemic phase of the disease starts, heralded by fever and visceral involvement. In this phase the disease can aff ect multiple systems, for example hepatic, renal, haematological, and respiratory. Organs are aff ected through damage to capillary endothelium and vasculitis caused by the spirochaete. Most patients become asymptomatic after a week of symptoms. After an interval of 3–4 days the immune phase of the disease starts, the hallmark of which is appearance of antibodies in the serum. Some patients may again become symptomatic. It is in this phase that neurological manifestations occur; the immune response is the main cause of the neurological defi cits. Neuroleptospirosis occurs in about 2% of patients, with aseptic meningitis being the most common neuro logical manifestation. Other presentations include myeloradiculopathy, myelopathy, Guillain-Barré syn drome-like presentation, meningoencephalitis, intra cerebral bleeding, cerebellar dysfunction, iridocyclitis, and tremor or rigidity. Cerebellar involvement occurs in about 3% of neuroleptospirosis cases. Neuroleptospirosis is under diagnosed, especially in an-icteric forms. In various studies leptospira was the cause of 5–40% of aseptic meningitis cases. Our patient presented with aseptic meningitis and cerebellar involvement. Unlike acute Japanese encephalitis or herpes encephalitis, which lead to signifi cant morbidity and mortality, neuro leptospirosis usually has a good prognosis; seizures and coma herald a poor prognosis. Making an early diagnosis of neuroleptospirosis is essential, since eff ective and specifi c treatment is available and can minimise sequelae.

Correlation of Serum Endothelial Dysfunction Markers with CT Angiographic Findings in Ischemic Stroke

Abstract Objective Endothelial dysfunction is considered as root cause of vascular diseases like stroke, myocardial infarction (MI) and venous thromboembolism. Soluble endothelial dysfunction markers are emerging as surrogate markers of disease risk. We aim to correlate the findings of Computed Tomography Angiography (CTA) with biochemical markers of endothelial dysfunction in patients of stroke. Material and method 40 patients diagnosed to have ischemic stroke or Transient Ischemic Attack (TIA) based on clinical history, examinations and imaging were included. We assessed high sensitive C – reactive protein (hsCRP), total nitric oxide (NO) and superoxide dismutase (SOD) levels in all patients within 24 hours and CT-Angiography of bilateral neck vessels within 48 hours of hospital admission. Results Increase in hsCRP, NO and decrease in SOD was significant in cases as compared to controls. These biochemical markers correlated significantly with CT Angiographic findings. Conclusions This study demonstrates that hsCRP, NO and SOD is good surrogate biochemical markers for assessing disease risk and burden in ischemic stroke. These surrogate markers showed a linear correlation and statistical significance with CT angiography score. Specific intervention targeted to reduce the oxidative stress, as indicated by these markers, and imaging findings should be a part of stroke management protocol.

A rare case of Balo concentric sclerosis showing unusual clinical improvement and response with oral prednisolone

The present report is a rare case of Balo Concentric Sclerosis. Most cases have either been diagnosed post mortem or have succumbed to the disease after being diagnosed ante mortem. In our case, the patient showed a dramatic response to treatment, and after a one-year follow-up, he was asymptomatic, with no relapses or residual effect of the illness.

Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

Nonhealing Ulcer: Acroangiodermatitis of Mali

An 18-year-old male presented with a nonhealing wound on left lower limb, pain and swelling over multiple joints, weight loss, and yellowish discoloration of eyes and urine for the past 4 years. On examination, the patient had pallor, icterus, and generalized lymphadenopathy with a nonhealing unhealthy ulcer over left medial malleolus. He had deformed joints with hepatomegaly and splenomegaly. His laboratory investigations were positive for antinuclear antibody (ANA) and anticardiolipin antibody (ACLA). Synovial fluid analysis showed inflammatory findings. Biopsy of margin of the ulcer showed findings consistent with Acroangiodermatitis of Mali. The patient was treated with disease-modifying antirheumatic drugs (DMARDs) and aspirin for juvenile idiopathic arthritis and secondary antiphospholipid antibody syndrome (APS), respectively. The ulcer was managed conservatively with systemic antibiotics and topical steroids along with limb elevation and compression elastic stockings. The patients symptoms improved significantly, and he is in our followup.

Fever, rash, and crusting ulcers.

1576 www.thelancet.com Vol 373 May 2, 2009 In August, 2008, a 14-year-old boy presented to our outpatient department complaining of fever and swellings in the neck for the past 2 months, rash for 1·5 months, and nasal regurgitation for 15 days. The high-grade intermittent fever appeared daily without diurnal variation; many, small, non-tender glandular swellings appeared bilaterally in the neck when the fever started. Non-pruritic red-brown macules appeared on his skin, which later turned into papules and blisters, and then into small ulcers that crusted over (fi gure A). The process took 10–14 days. Skin lesions appeared in crops, with a new crop erupting every 8–10 days. At presentation, there were lesions in all stages of development. There was no relevant medical history. The young boy had been prescribed antibiotics and treatment for tuberculosis by local low-resource facilities but had no response. On examination, he was pale and had several enlarged cervical lymph nodes (2–4 cm) bilaterally. His soft palate was ulcerated with necrotic base, causing velopharyngeal incompetence. Many ulcers, 1–2 cm in size, with central crusting, were present on his limbs (predominantly on the fl exor aspects of the lower limbs), trunk, and back; face, scalp, palms, and soles were spared. Some red-brown macules and haemorrhagic blisters were also present. Systemic examination was normal. Laboratory blood tests showed a normocytic normochromic anaemia (haemoglobin 79 g/L) with no atypical lymphocytes; other test results were normal. Serology for HBV, HCV, and HIV was negative. Chest radiography and abdominal ultrasonography were normal. CT of the neck showed several small lymph nodes. Examination of a bone-marrow biopsy sample showed a normocellular marrow with no evidence of malignant disease or parasites. A biopsy sample of cervical lymph node showed preserved follicular architecture and dilated sinuses with proliferation of sinus histiocytes and tiny necrotic foci (not shown). Skin biopsy sample showed: dense superfi cial and perivascular wedge-shaped infi ltrate of lymphocytes; a hyperplastic epidermis; a dermoepithelial junction showing vacuolar change and scattered necrotic keratinocytes; and a crust of parakeratotic cells (fi gure B). The clinical features and histopathological fi ndings were suggestive of febrile Mucha-Habermann disease (a form of pityriasis lichenoides). We treated our patient with aciclovir and a course of corticosteroids, but he died 3 weeks after admission. Our patient most likely had febrile Mucha-Habermann disease. Although the skin histopathological changes strongly suggested this disease, for defi nitive diagnosis CD30 staining would be needed to diff erentiate it from lymphomatoid papulosis; this test was not done while the patient was alive. Distinguishing between the two conditions can be diffi cult; the clinical features that favoured a diagnosis of febrile Mucha-Habermann disease were the presence of systemic features, involvement of the oral cavity, and absence of any nodular lesions. By contrast, lymphomatoid papulosis has no systemic features, very rarely involves the oral cavity, and commonly presents with nodular lesions. The aetiology of pityriasis lichenoides is unclear; it may be a lymphoproliferative disorder, and infectious agents have also been implicated. It is characterised by erythematous, scaly papules, often accompanied by haemorrhagic and papulo-necrotic lesions. Febrile Mucha-Habermann disease is a variant characterised by acute onset of large, more destructive, coalescent ulceronecrotic skin lesions, with high fever and systemic symptoms including malaise, myalgia, arthralgia, and gastrointestinal and central nervous system symptoms. Prompt treatment with high-dose corticosteroids rapidly diminishes the infl ammatory component. Methotrexate, psoralen plus ultraviolet-A, antibiotics, aciclovir, dapsone, debridement, and skin grafting have also been used. Febrile Mucha-Habermann disease need not be fatal if it is diagnosed early and prompt treatment initiated. Our patient was from a poverty-stricken low-resource setting, highlighting that early tissue diagnosis can be crucial in some cases of pyrexia of unknown origin.

Atypical neurofibroma and osteosclerotic metastasis.

35-year-old male presented with multiple swellings in left leg, headache, weakness of limbs for 4 months, and blurring of vision for the last 15 days. On examination, he was pale, cachexic with generalized lymphadenopathy and lower motor neuron type weakness of limbs sparing right upper limb. Blood investigations showed anemia with high alkaline phosphatase. Chest radiograph revealed osteosclerotic metastatic lesion in humerus. Biopsy of leg lesion revealed atypical neurofibroma. Computed tomography (CT) of thorax revealed osteoblastic metastasis. Bone marrow aspiration showed cells with round to oval nuclei, fine granular chromatin with large central prominent nucleoli and eosinophilic cytoplasm with acini formation. Magnetic resonance imaging (MRI) of brain and spinal cord defined metastatic leptomeningeal deposits. Cerebrospinal fluid (CSF) cytology was positive for malignant cells. Gastroscopy showed an ulceroinfiltrative growth from stomach which on histopathology revealed diffuse adenocarcinoma. Palliative treatment was given with intrathecal methotrexate and systemic corticosteroid with chemotherapy. Patients symptom improved drastically, but we lost him to followup.