Marcos R.G. de Freitas

Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of vascular lesions and usefulness of nerve studies in the detection of persistent bacilli.

Abstract Nerve biopsy specimens from 53 patients with leprosy and neuropathy were taken from the sural, the dorsal branch of the ulnar, or the superficial radial nerves and processed for light and electron microscopy. There was inflammation in 40 cases (75%), 7 with a granulomatous reaction, various stages of fibrosis in 35 (66%), and endoneurial vascular neoformation in 7. In two cases, small focal infarcts were associated with marked endoneurial inflammation compressing the vessels, in addition to endoneurial lymphocytic vasculitis. Most had an axonal neuropathy of varying degree, some with total fibre loss, others with predominant small myelinated and unmyelinated fibre loss. Signs of demyelination and remyelination were the main findings in 9 cases (17%). Bacilli were present in endothelial, perineurial, Schwann cells and in macrophages. On two occasions, they lost their alcohol acid resistance, were suspected in semithin sections, and confirmed ultrastructurally. The biopsy was decisive for the diagnosis of leprosy in 15 cases (28%), most without skin lesions. We evaluated the effectiveness of the treatment in 20 (37.7%), 12 without and 8 with bacilli, despite negativity in the skin. The diagnosis of leprosy based on skin lesions was confirmed with the nerve biopsy in 9 cases, 6 had an inflammatory neuropathy suggestive of leprosy in the absence of bacilli, and 3 had nonspecific changes in the sural nerve since the neuropathy was in the upper limbs. We conclude that nerve biopsy is indicated for the diagnosis of leprosy in cases without clinically visible skin lesions and to evaluate the effectiveness of the treatment. In these cases the ultrastructural studies are important for recognition of the bacilli. Vascular lesions may play an important role in the progression of the nerve damage, including the occurrence of focal nerve infarcts which, to our knowledge, have not been previously reported in association with leprosy.

Review of the etiologies of viral meningitis and encephalitis in a dengue endemic region.

OBJECTIVES To evaluate the etiology of viral meningitis and encephalitis in adults and adolescents living in areas affected by dengue. METHODS Over two years, adults and adolescents with diagnoses of viral encephalitis or meningitis were selected for study in Brazil. PCRs for dengue, enterovirus, HSV1 and 2 and cytomegalovirus were performed in CSF samples. Serum and CSF samples were tested for the presence of anti-dengue IgM antibodies. RESULTS The etiologies of encephalitis and meningitis were determined in 70% of cases (30/47). Dengue was the leading cause of encephalitis (47%) with normal CSF cellularity in 75% of these patients. HSV1 was found in 17.6% of the cases, two of which had mild encephalitis. Enterovirus was the most common cause of meningitis (50%), followed by HSV1 (15%), cytomegalovirus and dengue (10%, each). CONCLUSIONS We identified the viral agents causing encephalitis and meningitis in a higher proportion of cases than has been reported in other studies. Dengue was the most frequent cause of encephalitis, which surpassed HSV. In endemic areas, dengue should be investigated as an important cause of encephalitis. Normal CSF cellularity should not exclude dengue encephalitis. Enterovirus is known to be the leading cause of meningitis in children, but here we found it was also the main cause of the disease in adults. HSV1 should be investigated in patients with mild forms of encephalitis and meningitis.

Meningitis determined by oligosymptomatic dengue virus type 3 infection: Report of a case

Dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. Neurological manifestations such as encephalitis, myelitis, Guillain-Barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. Meningitis is a rare complication. We report the case of a 24-year-old woman who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with a normal glucose value and negative bacterial and fungal cultures. The etiology of meningitis was confirmed by positive dengue PCR in the serum. This case report highlights dengue infection as a potential cause of meningitis in endemic areas. Also, meningitis can be the first manifestation of the infection. Dengue should be investigated even in the absence of a typical picture of the infection.

Amyotrophic lateral sclerosis: new perpectives and update

Amyotrophic lateral sclerosis (ALS), Charcot’s disease or Lou Gehrig’s disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades – or even one decade – ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion.

Oligosymptomatic dengue infection: a potential cause of Guillain Barré syndrome

BACKGROUND Dengue infection may cause neurological manifestations such as encephalitis, myelitis, mononeuropathies, acute disseminated encephalomyelitis, and Guillain Barré syndrome (GBS). In endemic regions, the infection course can be oligosymptomatic making difficult the diagnosis of the neurological picture associated with dengue infection. OBJECTIVE To report dengue infection and GBS association, even in oligosymptomatic cases of this infection. METHOD During the dengue epidemic in Rio de Janeiro city we looked for GBS cases, testing IgM antibodies for dengue and dengue polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) and serum. RESULTS We report seven cases (46.6%), presenting dengue positive IgM in serum but with poor or without clinical symptoms of the previous infection. Two of them had also positive IgM antibodies in CSF. CONCLUSION These data show that search for dengue infection should be a routine in GBS cases living in endemic areas.

Benign monomelic amyotrophy: a study of twenty-one cases

A consecutive series of 21 patients with single limb atrophy (monomelic amyotrophy) is reported. Sixteen had lower limb atrophy and five had upper limb involvement. The median age of the onset was 20 years. Characteristic features were sporadic occurrence, wasting confined to one limb, insidious onset with slow progression, stabilizing in 1 to 4 years, and absence of pyramidal signs. All the patients with upper limb involvement were male, however in our cases with lower limb amyotrophy there were no male preponderance. We observed wasting of the entire length of the lower limbs in six patients. There were nine cases with amyotrophy restricted to the leg and one with amyotrophy only in the thigh. In the upper limb in four cases the involvement was distal and in one patient the atrophy was proximal. The electromyographic features were suggestive of anterior horn disease not only in the affected limb but also, in some cases, in clinically uninvolved limb. Cervical or lumbar MRI was normal. MRI of the lower limb disclosed increased signal intensity in the gastrocnemius and soleus muscles in one patient suggesting denervation.

Guillain-Barré syndrome and head trauma: case report

The authors report the case of a 29 years old male patient presenting classical Guillain-Barré syndrome following head trauma. Only one other similar case is described in the literature. Head trauma as a precipitating event of the disease is discussed.

Tapia's syndrome caused by Paracoccidioidis brasiliensis

Tapias syndrome is due to extracranial involvement of the XIIth nerve and the recurrent laryngeal branch of the Xth nerve. There is ipsilateral paralysis of vocal cords, soft palate and tongue. The main causes are parotid and other tumors or injuries to the high neck. We describe here a Brazilian female patient who presented with a lesion in the nasal mucosa, and soon after had dysphagia and dysphonia. Examination revealed paralysis of the soft palate, vocal cords and tongue ipsilaterally. Microscopic examination of the lesion in the nasal mucosa revealed the presence of the fungus. The patient was treated with sulfonamide and ketoconasol.

Paralisia do nervo ulnar na lepra sem alterações cutâneas: biópsia do ramo superficial do nervo ulnar na mão

Leprosy is one of the most common diseases of peripheral nerves in the world. In Brazil it is particularly frequent, being a major health problem. In tuberculoid leprosy the ulnar nerve is the most common affected nerve. Sometimes there are no skin changes. In these cases in spite of nerve thickening only the nerve biopsy is capable to make a specific diagnosis. We performed a biopsy in the dorsal sensory branch of the ulnar nerve in the hand in 17 patients with ulnar palsy with thickening of the nerve in the elbow, without skin changes. The pathological findings consisted mainly of: loss of fibers (14 cases), inflammatory infiltration (13), fibrosis (12), demyelination and remyelination (9), presence of granuloma (6) and presence of bacilli (5 cases). We conclude that in case of ulnar nerve palsy in leprosy without skin changes, the biopsy of the dorsal sensory branch of this nerve in the hand is a good procedure for the diagnosis of leprosy.A lepra constitui causa frequente de acometimento de nervos perifericos, em nosso meio. O sistema nervoso periferico e acometido por vezes sem que haja alteracoes cutâneas: e a chamada forma neuritica pura. Nessa variante, o nervo mais afetado e o ulnar. Nos casos de acometimento isolado de nervos perifericos somente a feitura de biopsia de nervo conduzira ao diagnostico. Assim, resolvemos realizar biopsia do ramo sensitivo superficial do nervo ulnar na mao em 17 pacientes com paresia ou paralisia desse nervo e espessamento do mesmo na altura do cotovelo. Os principais achados foram: reducao do numero de fibras mielinicas em 14 casos, infiltrado inflamatorio em 13, fibrose em 12, desmielinizacao e remielinizacao em 9, presenca de granuloma em 6 e visualizacao do Mycobacterium leprae em 5. Concluimos que a biopsia do ramo sensitivo superficial do nervo ulnar na mao e um bom meio diagnostico de lepra em pacientes com acometimento desse nervo

Leprosy late-onset neuropathy: an uncommon presentation of leprosy

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON.