脑室-腹腔分流术治疗结核性脑膜炎并发脑积水

目的探讨脑室-腹腔分流术(VPS)治疗结核性脑膜炎(TBM)合并脑积水的效果。方法回顾性分析2004年1月至2010年7月行VPS治疗的15例TBM合并脑积水患者的临床资料。结果 15例患者全部行VPS,术后意识均好转、症状减轻,未发生结核性腹莫炎。术前抗结核治疗1月以上者10例,均无分流管堵塞发生;而另外5例抗结核治疗不足1月者,分流管堵塞者2例。脑脊液蛋白含量在0.5g/L以上者6例中2例堵管;脑脊液蛋白在0.5g/L以下的9例中,无堵管者。结论 VPS是治疗TBM并发脑积水的有效方法,术前最好能抗结核治疗1月以上。     

Use of urokinase in the treatment of tuberculous meningitis hydrocephalus

We present a patient with hydrocephalus after tuberculous meningitis successfully treated with urokinase. She presented with multiple episodes of headache, fever, and vomiting. She underwent external ventricular drainage and was treated with urokinase in addition to dexamethasone, acetazolamide, and 4 antituberculous drugs. She was evaluated clinically, radiologically, and by laboratory work-up. On short-term clinical follow-up (3 months), she was asymptomatic after the treatment with urokinase. She was radiologically evaluated 3 weeks after the treatment. An MRI of the brain showed a decrease in ventricular size. Urokinase can be considered as a safe and promising adjunctive treatment for tuberculous meningitis hydrocephalus.     

Normal ventricular-CSF may comfound the diagnosis of tuberculous meningitis hydrocephalus

BACKGROUND: The standard procedure for the diagnosis of central nervous system (CNS) infections consists of cerebrospinal fluid (CSF) sampling, which is usually accomplished by a lumbar puncture. However, in some patients presenting with acute hydrocephalus submitted to immediate CSF drainage, the fluid is customarily obtained from the placed draining system. In addition, the CSF obtained from the ventricular and lumbar spaces in some cases may show unusual differences, both in physiological and pathological conditions. ILLUSTRATIVE CASES: We report two children who presented with confounding results in the initial studies of their ventricular and lumbar CSF who were subsequently diagnosed with tuberculous meningitis, causing delay in diagnosis and treatment. AIM. By reporting these cases, we wanted to alert the treating physician about the possibility of this discrepancy to avoid the delayed diagnosis and management of the affected patients. DISCUSSION: We comment on the possible pathophysiological mechanisms that may result in this dissociation in ventricular and lumbar CSF composition. CONCLUSIONS; Normal results in CSF studies, especially those of the ventricular fluid, do not always rule out the presence of tuberculous meningitis. We suggest obtaining a CSF sample from the lumbar subarachnoid space in doubtful, or suspicious, cases of CNS infection even in the presence of a normal ventricular CSF.     

Management of intracranial pressure in tuberculous meningitis

Tuberculous meningitis (TBM) remains a common serious neurological emergency—especially in the developing world. Elevated intracranial pressure (ICP) is often a feature of severe TBM and is associated with high morbidity and mortality. The pathology associated with TBM, such as cerebral edema, hydrocephalus, tuberculoma(s), and infarcts related to arthritis, contribute to increase in intracranial volume and, therefore, elevated ICP. The three types of edema (vasogenic, cytotoxic, and interstitial) may contribute to cerebral edema. The molecular mechanisms underlying the events that ultimately lead to brain damage and cerebral edema during infection are complex. Similarly to bacterial meningitis, cerebral blood flow autoregulation is probably impaired in TBM, and the mechanisms are unclear. Although no universal guidelines are available to institute ICP monitoring in patients with severe TBM, it is be prudent to monitor patients at risk for increases in ICP. Such an approach helps to detect the secondary brain insults, allowing for a more informed approach to treatment. Treatment of elevated ICP involves a multipronged approach. The first step should be to identify focal brain lesions and hydrocephalus (which require surgical intervention) by brain imaging. Cerebral edema is treated with hyperosmolar agents. Mannitol is currently the most commonly used agent. It appears that use of hypertonic saline as an osmotic agent in infection-related cerebral edema has certain advantages. However, this needs to be established by well-designed trials. Use of steroids reduces not only cerebral edema but also the production of cytokines and other chemicals involved in the immunopathogenesis of TBM. Fever associated with TBM should be aggressively treated, because fever can worsen the impact of elevated ICP. Hyponatremia may complicate TBM and requires appropriate correction because it can aggravate cerebral edema.     

Use of intrathecal hyaluronidase in the management of tuberculous meningitis with hydrocephalus

A preliminary study to evaluate the efficacy of intrathecal hyaluronidase was carried out in nine children suffering from tuberculous meningitis with communicating hydrocephalus. This was followed by a randomized trial in which five cases were treated with intrathecal hyaluronidase, while six cases were treated by the insertion of a ventriculoperitoneal shunt. No untoward reaction of any significance was noted. The results were judged in terms of improvement in the sensorium and mentation, in specific neurological deficit (e.g., visual impairment and hemiparesis), and in overall functional performance. Although most of the patients receiving hyaluronidase showed some improvement in the sensorium, only one of the nine preliminary cases and one of the five cases in the randomized trial showed a total recovery of function. Two of the six shunted patients, however, showed complete recovery. Shunt insertion led to further improvement in two of the nine preliminary cases who had failed to respond to treatment with hyaluronidase. This preliminary study shows that intrathecal hyaluronidase does, in most cases, lead to an improvement in the sensorium but does not offer any particular advantage over shunt insertion in terms of regression of specific neurological deficit or overall functional improvement.     

Stroke in tuberculous meningitis

Stroke in tuberculous meningitis (TBM) occurs in 15-57% of patients especially in advance stage and severe illness. The majority of strokes may be asymptomatic because of being in a silent area, deep coma or associated pathology such as spinal arachnoiditis or tuberculoma. Methods of evaluation also influence the frequency of stroke. MRI is more sensitive in detecting acute (DWI) and chronic (T2, FLAIR) stroke. Most of the strokes in TBM are multiple, bilateral and located in the basal ganglia especially the 'tubercular zone' which comprises of the caudate, anterior thalamus, anterior limb and genu of the internal capsule. These are attributed to the involvement of medial striate, thalamotuberal and thalamostriate arteries which are embedded in exudates and likely to be stretched by a coexistent hydrocephalus. Cortical stroke can also occur due to the involvement of proximal portion of the middle, anterior and posterior cerebral arteries as well as the supraclinoid portion of the internal carotid and basilar arteries which are documented in MRI, angiography and autopsy studies. Arteritis is more common than infarction in autopsy study. The role of cytokines especially tumor necrosis factor (TNFα), vascular endothelial growth factor (VEGF) and matrix metaloproteineases (MMPs) in damaging the blood brain barrier, attracting leucocytes and release of vasoactive autocoids have been suggested. The prothrombotic state may also contribute to stroke in TBM. Corticosteroids with antitubercular therapy were thought to reduce mortality and morbidity but their role in reducing strokes has not been proven. Aspirin also reduces mortality and its role in reducing stroke in TBM needs further studies.     

Multidrug-resistant tuberculous meningitis

Multidrug-resistant tuberculous meningitis is now appearing worldwide, including in the United States, and is difficult to diagnose and treat. We discuss methods to diagnose tuberculous meningitis, review current and experimental assays for determining drug resistance, and consider approaches to management of the patient. We review the epidemiology of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis in both pulmonary and meningeal infections, discuss promising molecular methods for determining drug resistance, and review current approaches toward treatment of patients. The incidence of multidrug-resistant tuberculous meningitis is increasing, and diagnosing and treating these patients will be a major challenge. There is a need to improve rapid methods of isolating the organism from cerebrospinal fluid, to advance molecular methods to rapidly test the isolate for antibiotic sensitivity, and to develop new antituberculosis drugs, especially ones that cross the blood-cerebrospinal fluid barrier.     

Endoscopy for tuberculous hydrocephalus

Introduction The role of endoscopy in hydrocephalus due to infectious aetiology is unclear. Tuberculous hydrocephalus is a useful model to study because it presents particular challenges and the pathophysiology of the cerebrospinal fluid disturbance is well known.Materials and methods We present the results of 24 endoscopic operations in tuberculous meningitis.Result Endoscopic third ventriculostomy (ETV) was attempted in 17 patients: seven were successful, five failed, and five were not completed due to abnormal anatomy. There were five fenestration procedures, three of which were successful. Endoscopic biopsy of two tuberculomas failed to yield a bacteriological result. These operations were more difficult to perform than for hydrocephalus due to other aetiologies.Conclusion Although ETV is technically possible in this situation, it is imperative that the patients are adequately selected for the procedure to ensure optimal treatment and that the surgeon has experience with difficult cases.     

Treatment of tuberculous meningitis

INTRODUCTION: Tuberculous meningitis and brain tuberculomas are currently rare in the western world but remain serious. Improved outcome requires early recognition and treatment of these conditions. STATE OF ART: Treatment is usually begun before diagnostic confirmation. Therapeutic principles are now better defined thanks to recent recommendations and studies. Antituberculous therapy begins with two months of a combination of four drugs: isoniazid, rifampicin, ethambutol and pyrazinamid. Then follows a longer phase of bitherapy with isoniazid and rifampicin, lasting at least four months but usually extended to seven or ten months as a precaution. Patients at risk of toxic neuropathy should receive pyridoxine supplementation. Corticosteroids must be systematically added during the first eight weeks of treatment, beginning with high dose before progressive tapering. Hyponatremia is common, often induced by emesis and cerebral salt wasting syndrome. Therefore saline supply rather than water restriction is required. Non-obstructive hydrocephaly can usually be managed with diuretic therapy including acetazolamid, sometimes complemented by serial lumbar punctures. Neurosurgical interventions are rarely needed. Monitoring of treatment tolerance and efficacy is mainly clinical. Central nervous system imaging and cerebro-spinal fluid analysis are only required to explain clinical deterioration. CONCLUSION: With adequate and prompt anti-tuberculous, anti-inflammatory and supportive treatment, the prognosis of central nervous system tuberculosis can be greatly improved.     

Effects of the implantation of Ommaya reservoir in children with tuberculous meningitis hydrocephalus: a preliminary study

Objective

The role of Ommaya reservoir implantation in children with tuberculous meningitis hydrocephalus (TBMH) has been seldomly reported. Therefore, we performed this study to determine the role of the Ommaya reservoir in the treatment of children with TBMH.

Methods

We retrospectively analyzed the effects of Ommaya reservoir implantation in 12 children with TBMH. Intracapsular puncture of the reservoir was performed for draining the cerebrospinal fluid and the TBM was treated by intraventricular injection of isoniazid.

Results

The ideal treatment outcome was observed in nine (75?%) of the 12 children; two (16.7?%) children developed serious disabilities and one of them (8.3?%) eventually died. The treatment method was effective for all six (100?%) children with Palur grade II TBM but showed no effect in three (50?%) children with grade III and IV TBM. The number of leukocytes in the cerebrospinal fluid decreased to 20?×?10⁶/L (75?%) within 2?weeks after implantation of the reservoirs. Finally, the Ommaya reservoirs in eight children were removed but were retained in four children. Four children had to undergo ventriculoperitoneal shunt.

Conclusion

Ommaya reservoir implantation has been shown to be effective in treating children with TBMH. This method may be largely suitable for children with early grade II TBM or partly in children with grade III TBM who have mild or moderate hydrocephalus that can alleviate after short-term treatment. Thus, a good proportion of children who undergo Ommaya reservoir implantation can avoid ventriculoperitoneal shunt surgery.     

Experimental tuberculous meningitis in rabbits

Summary Rabbits sensitized by intraperitoneal injections of tubercle bacilli and later showing positive skin reactions to tuberculin, as well as non-sensitized rabbits, were given a single inoculation with live tubercle bacilli into the cisterna magna. The animals' brains were examined histologically, 2 to 27 days following the inoculation, for a comparative study of local reactions and their temporal sequence. It was found that in both sensitized and non-sensitized rabbits the major reactions of the brain were histologically similar in type but differed in intensity, in the time of their appearance and in the intervals between them. These reactions were more severe and, on the whole, slower in appearance in the non-sensitized animals and consisted of phagocytosis of tubercle bacilli by activated local histiocytes, the appearance of acute, non-specific inflammation with components of tissue hypersensitivity, tubercle formation by epithelioid cells and caseation, in that order of sequence. These reactions were evoked not only in the cerebral leptomeninges, but also, and simultaneously, in the perivascular reticular tissue of intracerebral, intraneural and choroid-plexus blood vessels. It thus appears that tuberculous involvement of the brain parenchyma, cranial nerves, ependymal lining and choroid plexuses in tuberculous meningitis may not be a complication but a common manifestation of that process.

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Zusammenfassung Kaninchen, die mit intraperitonealen Injektionen von Tuberkelbacillen sensibilisiert waren und daraufhin positive Hautreaktionen auf Tuberkulin zeigten, und nicht sensibilisierten Kaninchen wurde eine einmalige Injektion von lebenden Tuberkelbacillen in die Cisterna magna verabreicht. Die Tiergehirne wurden (2–27 Tage nach der Beimpfung) zum Zwecke der vergleichenden Untersuchung der Lokalreaktionen und deren zeitlicher Folge histologisch untersucht. Es wurde gefunden, daß in beiden Fällen, also sowohl bei den sensibilisierten als auch bei den nichtsensibilisierten Kaninchen die Hauptreaktionen des Gehirns in der Zeit ihres Auftretens und in den Intervallen histologisch ähnlich, jedoch dem Grade nach verschieden waren. Diese Reaktionen waren schwerer und vor allem von langsamerer Manifestation bei den nichtsensibilisierten Tieren und bestanden in Phagocytose der Tuberkelbacillen durch aktivierte ortständige Histiocyten. Auftreten von akuter, unsperifischer Entzündung mit Komponenten der Gewebsüberempfindlichkeit, Tuberkelbildung aus epithelioiden Zellen und Verkäsung in dieser Reihenfolge. Diese Reaktionen wurden nicht allein in den Gehirnmeningen hervorgerufen, sondern auch — gleichzeitig — im perivasculären retikulären Gewebe der intracerebralen, intraneuralen und der Plexus-Blutgefäße. Es scheint also, daß der tuberkulöse Befall des Gehirnparenchyms, der Hirnnerven, des Ependyms und des Plexus bei tuberkulöser Meningitis nicht eine Komplikation, sondern eine übliche Manifestation im Rahmen des Grundprozesses darstellt.

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Supported by the Hadassah Medical Organization and the Scheider Neuropsychiatric Funds.     

Chronic untreated tuberculous meningitis

Summary We describe a 34-year-old man who suffered from tuberculous meningitis for 2 years without receiving antituberculous medication. Our case is compared with other forms of indolent or benign variants of the disease.     

Seizure heralding tuberculous meningitis

Seizures may frequently occur during tuberculous meningitis. We describe a patient with an apparent generalised tonic-clonic seizure, initially not associated with any magnetic resonance imaging (MRI) abnormality, which was the presenting symptom of tuberculous meningitis. Follow-up MRI, performed after gadolinium administration, showed signs of meningeal involvement. Seizures may be the presenting symptoms of tuberculous meningitis even in the absence of evident intracerebral lesions on MRI. Therefore, contrast-enhanced brain MRI should be performed in the diagnostic workup for each first seizure, especially in patients with a clinical suspicion of CNS infectious disease. The term "heraldic seizure", indicating a subset of acute symptomatic seizures presenting at the onset of a brain/systemic injury or preceding the full clinical manifestation of a cerebral insult, may be helpful to classify these seizures retrospectively, based initially on unknown aetiology.