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Abstract
Granulomatous inflammation is a distinctive pattern of chronic inflammation due to infectious or non infectious agents. Its formation is due to the cell mediated immune response to such agents (Mitchell and Cotran, 2003; Dov, 2003).
Granulomatous inflammatory disorders involving the CNS have a wide variety of etiologies, clinical presentations, overlapping with each other and with other CNS disorders. And up till now, they have non conclusive investigations results making rapid accurate diagnosis sometimes difficult or impossible without tissue biopsy. Also many medical specialties are involved in the management of such cases, which leads to a lack in comprehensive integrated approach (Metwally, 2006).
Tuberculosis remains a major global problem and a public health issue of considerable magnitude, and was declared as a global emergency in 1993 by the World Health Organization (WHO). This was due to spread of HIV and multiple antituberculus drug resistance (Dolin et al., 1994). Common presentations of CNS tuberculosis include basal meningitis, focal cerebral lesions, myelopathy, Pott’s disease, rarely myelitis. In young age it may present with rapid onset encephalopathy (Dastur et al., 1995)
Rapid diagnosis of CNS TB is difficult, and usually Treatment is started on clinical assumption. Diagnostic studies, mainly smear examination and culture have low sensitivity and are time consuming (Muralidhar, 2004), while the PCR has higher sensitivity, yet it is not technically and financially available in many endemic areas. Most common imaging studies findings are hydrocephalus and basal meningitis, which is not specific (Chang et al.,1990).
Treatment should start with quadruple therapy, and in cases of INH resistance, it should be replaced by Ethambutol. Steroids should be used in cases of clinically or radiological evident of meningeoencephalitis or increased CSF pressure to more than 300 cc H2O. Prognosis is related to the severity of meningeoencephalitic symptoms at the start of treatment. It should be noted that the most common causes of treatment failure is multiple drug resistance and poor compliance (Daikos et al.,2003).
Fungal infections or the CNS has increased recently due to increase prevalence of HIV and immunosuppressive states specially that is related to organ transplantation. Diagnosis is mostly a clinical surprise, and it requires a high index of suspicion. The most common CNS fungal infection is Cryptococcosis. It is specially prevalent in the HIV seropositive population with 20% of HIV mortality cases due to crypotcoccal meningitis.
cryptococcus usually spreads from a pulmonary focus with high tendency to affect the CNS, and is protected from the immune system by a polysaccharide capsule. The most common clinical presentations are headache, fever, increased inctracranial tension and blindness. The definitive diagnostic test is CSF examination with India ink stain showing the cryptococci. It is treated with amphoteracin B and Flucytosine (Jermey, 2004).
Aspergillosis is another form of fungal infection that can spread to the CNS either hematogenously from the lung or by direct invasion from the nasal sinuses. Unlike cryptococcosis, it is specially prevalent in cases of organ transplantations clinical features vary from diffuse presentation of meningitis and increased ICT to focal lesions. It characteristically invade cerebral vessels and adjacent brain parynchema, causing thrombosis and secondary haemorrhagic infarcts. It generally has poor prognosis which varies according to patient immunity, in cases of markedly suppressed immunity it is fatal within few weeks, otherwise it may develop to granulomas, abscesses evident as ring enhancing lesions in radiological studies (enhancement = immunity). Definitive diagnosis require brain biopsy. Treatment should be stared as early as possible, and it includes surgical debridement with adequate safety margin (to avoid postoperative cerebrovascular complications) and administration of amphoteracin B and flucytosine, in addition to correcting the general condition (immune reconstitution). Recently voriconazole has shown promising results when combined with surgery (Sepkowitz et al., 1997).
Rhinocerebral Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients, manily diabetics. These infections are becoming increasingly common, yet survival remains very poor, as many cases are diagnosed late and treatment stratigies based on available antifungals and surgical depridement with control of risk factors are not effective (Brad et al., 2005).
Invasive candidal CNS infection is more common in premature infants and neonates, and present usually by meningitis with insidious vague clinical picture (lethargy, confusion), and it is also treated with amphoteracin B and flucytosine (Burgert et al., 1995).
There has been an increased awareness of the parasitic CNS infection in the last few decades. Cysticercosis, on of the common parasitic infections, was frequently under diagnosed due to the lack of adequate diagnostic tools, and even after the advent of modern neuroimaging techniques, it was frequently misdiagnosed as TB. Viable CNS cisticerci don’t induce an immune reaction and are frequently asymptomatic, while the immune system is stimulated by the dying organism, leading to the development of the clinical manifestations of the illness (fits, hydrocephalus). This has provoked an unsettled debate about the necessity of use of paraciticidal drugs in asymptomatic patients. Solid diagnosis is difficult except by tissue biopsy, MRI showing cysts with scolices, or subretinal scolices on fundoscopy. Recently EITB has proved to be 100 % specific (Carpio et al., 1998).
Toxoplasmosis is another form of parasitic CNS infection. It commonly presents with afebrile focal cerebral lesions, commonly ganglionic, cerebellar and brain stem. When manifest in an HIV Patient, it presents with encephalitis, fever and disseminated multi organ affection. Diagnosis is difficult, serology and PCR are not sensitive. Radiological studies show multiple brain enhancing lesions which when combined with positive serology empirical treatment (pyrimethamine + leucoverin) should be started and if there is no response in 2 weeks, a tissue biopsy should be obtained (Luis, 2006).
In hydatid disease, 5% of cases have CNS affection, in the form of space occupying lesions presenting clinically as increased ICT, fits of focal cerebral lesions. Imaging studies show a cystic brain lesion with no enhancement. Diagnosis rests on the evidence of systemic affection, and ELISA is done in doubtful cases. Treatment is surgical excision under albendazole cover (Eckert et al., 2001).
Bilharziasis affect the CNS in 1% of cases, through granulomatous inflammation around ova deposited in brain and spinal cord. It present by myelopathy, meningeoenchephalitis, optic neuritis and rarely space occupying lesion. It is diagnosed by demonstrating ova in urine, stool or rectal biopsy, also ELISA is 99% specific. Brain imaging reveals central linear enhancement surrounded by central punctuate nodules. It is treated by praziquantel or oxamniquine (David et al., 2004).
Sarcoidosis is a granulomatous inflammation of unknown etiology. And neurological manifestations occur in 5 – 16% of patients, usually with correlation to disease activity. Isolated neurosarcoidosis is reported in less than 10 % of cases (James, 1998). Although neurosarcoidosis can affect any part of the central or peripheral nervous system, the most common presentations are, aseptic basal meningitis, multiple cranial neuropathies usually facial and optic nerves, focal supratentorial parenchyma involvement, axonal polyneuropathy and poly neuritis multiplex (Waxman and Sher, 1979).
Neurosarcoidosis is a diagnosis of exclusion. It relies on the systemic features if present. The most diagnostic investigation is tissue biopsy (Transbronchial mediastinal biopsy, skin, superficial lymph nodes, parotid). The combination of positive gallium scan and elevated serum ACE is a highly diagnostic non invasive tool (83 to 99% specificity). In cases of isolated neurosarcoidosis, routine CSF studies and Neuroimaging are not conclusive. ACE level in CSF is elevated in 50 % of cases, otherwise we should rely on tissue biopsies for solid diagnosis (Bourahoui et al., 2004).
Treatment of neurosarcoidosis should start immediately with corticosteroids. Other steroid sparing agents (cyclosporine, azathioprine, methotrexate, cyclophosphamide) can be used to decrease maintenance doses of steroids, and in refractory cases. Newer agents as tacrolimus, sirolimus, anticytokine therapy are under trial (Vital et al., 1982).
Wegener granulomatosis (WG) is a unique clinicopathological disease entity characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract, segmental necrotizing glomerulonephritis, and small vessel vasculitis (Carol, 2003).
The reported frequency of neurologic involvement in WG ranges from 22% to 54%., and its manifestations are extremely varied. the most common neurological presentations are mononeuritis multiplex, cranial neuropathies, seizures, altered cognition (cerebritis), focal motor and sensory complaints, stroke syndromes, or diabetes insipidus (Metwally, 2006).
Routine laboratory investigations are not specific, yet testing for c-antineutrophil cytoplasmic antibodies (ANCA) is 97% specific for WG, and 90% sensitive for classical systemic disease. MRI findings include diffuse or focal thickening of the meningies with contrast enhancement, Nonhemorrhagic infarcts and occasionally Nonspecific white matter lesions (Joseph et al., 1999).. Glucocorticoids combined with cyclophosphamide or methotrexate are the only two regimens that have been shown to induce remission of active WG affecting a major organ (Hoffman et al., 1992).
Primary angiitis of the CNS is a rare disease characterized by vasculitis of small and medium arteries in the brain and spinal cord. Presentations are highly variable, but the triad of headache, organic brain syndrome, and multifocal neurologic deficits is most suggestive. Most affected patients do not have systemic symptoms, signs, or abnormal routine blood tests, including ESR (Bettoni et al., 1984).
Noninvasive tests have limited sensitivity and specificity. MRI is most sensitive, being abnormal in more than 80% of patients. The diagnosis is very rare when both the lumbar puncture (with regards to cells and protein level) and the MRI are normal. Angiography showing beading produced by alternating stenosis and dilation suggests the diagnosis but is not specific. Analysis of biopsy specimens of brain cortex and leptomeninges can help establish the diagnosis. In the absence of positive results on biopsy specimen analysis, the diagnosis of primary angiitis of the CNS should be doubted (Lie, 1992).
The best therapy has not been established many patients are treated with prednisone and cyclophosphamide (Scolding et al., 1997).
Histiocytosis is a rare blood disease that is caused by an excess of white blood cells called histiocytes. It mainly affects children with 76 % of the cases occurring before 10 years of age (Vassallo et al., 2000).
Clinically it affects the skin, bone, eyes, gastrointestinal tract, with diabetes incipidus being the hallmark of CNS affection. Others symptoms due to CNS affection include other endocrinal deficiencies and rarely behavioral changes or manifestations of increased ICT (Martin-Duverneuil et al., 2006).
MRI findings in histiocytosis include thickening of the pituitary stalk, dura based masses, white matter lesions and cystic changes in pineal gland (Daniela et al., 2004). No general recommendations concerning treatment are established till now. The individual strategy is dependent on the type and site of the lesions and the state of LCH outside the CNS. And chemotherapeutic agents like vinblastine, etoposide or mercaptopurine, together with steroids are being assessed. (Daniela et al., 2004)
Cholesteatoma and cholesterol granuloma are 2 destructive lesions affecting the temporal bone, with possible CNS complication secondary to local invasion. They can be diagnosed by CT scan, differentiated by MRI, and treated by different surgical approaches (Ferlito et al., 1997; Topalogue et al 1997; Chang et al., 1998).