Neurologic complications in inflammatory bowel diseases

Some inflammatory diseases of the gastrointestinal system are associated with neurological symptoms which, in rare cases, may precede the onset of the gastrointestinal manifestation of the disease. Celiac sprue is characterized by an intolerance to the wheat protein gluten. The typical neurological manifestation of celiac sprue is cerebellar ataxia. The ataxia as well as the gastrointestinal symptoms can be treated with a strictly gluten-free diet. The neurological symptoms of Whipple's disease, a disorder caused by gram-positive bacilli, are variable. Typical symptoms of cerebral Whipple's disease include dementia, ophthalmoplegia, movement disorders, and signs of hypothalamic dysfunction. Nowadays, the diagnosis of cerebral Whipple's disease is made by PCR detection of the bacilli in the CSF. Crohn's disease and ulcerative colitis are associated with neurological symptoms to a similar proportion. Various forms of polyneuropathies have been observed. The CNS manifestations of inflammatory bowel diseases include thromboembolic stroke, cerebral venous thrombosis, and cerebral vasculitis.     

Diagnostic work-up in Whipple's disease with cerebral involvement

The diagnostic work-up in the case of a suspected cerebral involvement of Whipple's disease involves neuroimaging and analysis of cerebrospinal fluid (CSF) including polymerase chain reaction (PCR) assays for Tropheryma whipplei. As neurological findings may be complex and unspecific, extracerebral symptoms often lead to the suspicion of Whipple's disease. We report the cases of two patients in whom the suspected diagnosis of Whipple's disease could not be proved either by endoscopy or by the analysis of CSF. Only by means of a cerebral biopsy was the diagnosis assumed and specific therapy was initiated.     

Whipple''s disease presenting as an isolated lesion of the cervical spinal cord

Chronic myelitis from Whipple's disease of the spinal cord is extremely rare. The differential diagnosis includes chronic inflammatory lesions, viral or bacterial infections, and tumours of the spinal cord. Here we present a 50-year-old man with mild sensory deficits because of a large lesion of the cervical spinal cord who markedly showed improvement during probatory antibiotic therapy. PCR and jejunal biopsy were initially negative and only later confirmed the diagnosis of Whipple's disease. Clinical and neuroradiological criteria are suggested which may be of help in the early diagnosis of spinal Whipple's disease before confirmation by molecular biology or histology.     

Cerebrospinal fluid ferritin in chronic hydrocephalus after aneurysmal subarachnoid hemorrhage

Objectives Subarachnoid hemorrhage (SAH) is a common cause of chronic hydrocephalus. Blood in the subarachnoid space is intracranially metabolized to bilirubin and iron, and free iron is thereafter detoxified by ferritin. However, no studies have reported the relationship between intracranial heme metabolism and chronic hydrocephalus after SAH. The goal of this prospective study was to clarify the relationship between intracranial heme metabolism and chronic hydrocephalus after SAH. Methods The authors measured the levels of bilirubin, iron and ferritin in the cerebrospinal fluid (CSF) of 70 consecutive patients with aneurysmal SAH of Fisher computed tomography Group III, and determined the relationship between these substances’ levels and hydrocephalus requiring ventriculoperitoneal shunting. Results The CSF concentrations of ferritin and inflammatory cells were significantly higher in shunted patients (n = 27) than in non-shunted patients (n = 43) on Days 3 and 4 (p<0.05 in ferritin and p<0.01 in inflammatory cells) and 11 to 14 (p<0.005 in ferritin) post-SAH. These results were independent of other clinical factors. The occurrence of chronic hydrocephalus was not affected by the extent of the intracranial heme metabolism in terms of the bilirubin and iron levels. Conclusions This is the first study to show that patients who subsequently had chronic hydrocephalus requiring CSF shunting were associated with higher CSF levels of ferritin in the acute stage of SAH. Higher CSF ferritin levels may not reflect the amount of blood in the subarachnoid space that was intracranially metabolized, but rather more intense subarachnoid inflammatory reactions which may cause chronic hydrocephalus after SAH. Received in revised form: 19 January 2006     

Neurological complications of inflammatory intestinal diseases

A number of neurological symptoms have been described as complications of inflammatory bowel disorders such as coeliac disease, Whipple's disease, Crohn's disease and ulcerative colitis. The neurology of coeliac disease includes disorders of the central nervous system encompassing cerebellar ataxia, epilepsy, myoclonus, dementia and multifocal leukoencephalopathy. Peripheral neuropathies, of axonal and demyelinating types, and myopathies have also been reported. The pathomechanisms are more related to immunological-inflammatory processes than to a malresorptive vitamin deficiencies. While CNS symptoms of coeliac disease show a poor response to gluten restriction, peripheral symptoms may respond to elimination of gluten from the diet. There are few reports of a successful corticosteroid treatment in patients showing inflammatory findings in the CSF or bioptic material. Whipple's disease is caused by the gram-positive bacillus Tropheryma whipplei. Patients with a central nervous system manifestation of Whipple's disease may develop a variety of symptoms including dementia, supranuclear gaze palsy, movement disorders, hypothalamic dysfunction and myorhythmia. The CNS-infection is diagnosed by PCR of the CSF. Long-term antibiotic treatment is required, and relapses may occur after withdrawal of antimicrobial therapy. Crohn's disease and ulcerative colitis are complicated by various forms of polyneuropathies, and arterial and venous cerebrovascular diseases. In most cases with neurological complications of inflammatory gastrointestinal diseases an immune mediated inflammatory process is suspected to be the underlying pathomechanism.     

Postoperative communicating hydrocephalus in patients with supratentorial malignant glioma

Postoperative communicating hydrocephalus in adult patients with supratentorial malignant glioma is a relatively uncommon condition that occurs months after the initial operation of tumor excision. It occurred in only five of 50 consecutive cases treated in our department during the past 10 years. The hydrocephalus appeared to be attributable to leptomeningeal dissemination of tumor cells and subsequent impairment in cerebrospinal fluid (CSF) absorption. The tumors were located adjacent to the lateral ventricles in all five patients, and the proximity of the tumor to the cerebral ventricles may have facilitated dissemination of the tumor cells into the CSF space, resulting in hydrocephalus. The hydrocephalus was treated by a shunt surgery in all five cases, and the symptoms temporarily improved. None of the five patients experienced shunt malfunction or abdominal symptoms attributable to metastasis to the peritoneal cavity, and all five patients died of regrowth of the intracranial tumor or of pneumonia.     

Alteration of atrial natriuretic peptide and cyclic GMP in cerebrospinal fluid in canine kaolin-induced hydrocephalus]

CSF and Plasma concentrations of atrial natriuretic peptide (ANP) and cyclic GMP (cGMP), which is regarded as a second messenger of ANP, were measured intermittently during the progress of canine kaolin-induced hydrocephalus. Data were analyzed being divided into three groups, normal, acute (within 2 weeks after intracisternal injection of kaolin suspension) and chronic (from 3 to 4 weeks after injection of kaolin suspension) stages of hydrocephalus. The presence of ventricular dilatation was evaluated by MRI or postmortal dissection. ANP, cGMP in CSF and CSF pressure significantly increased in the acute stage of hydrocephalus. In the chronic stage, ANP in CSF and CSF pressure had no statistical difference with data of the normal stage. Cyclic GMP in CSF kept significantly high value in the chronic stage of hydrocephalus. CSF concentrations of Na, CSF osmolarity, plasma ANP, plasma cGMP, plasma ADH, serum Na and serum osmolarity did not change significantly in the course of hydrocephalus. There was a significant positive correlation between ANP in CSF and CSF pressure. ANP in CSF did not correlate with degree of ventricular dilatation. Cyclic GMP in CSF did not correlate with ANP in CSF, nor with CSF pressure. These data suggest that concentration of ANP in CSF may alter directly or indirectly depending on CSF pressure in kaolin-induced hydrocephalus. And cGMP in CSF was suggested to depend not on ANP in CSF, but on other unknown factors in kaolin-induced hydrocephalus.     

脑室镜三脑室造瘘术治疗小儿阻塞性脑积水

目的分析本组49例病例，就手术病种和年龄的选择、手术方法及技巧做一介绍。方法全组49例，年龄1个月-18岁，平均33个月。CT、MRI及^99Tc^m-DTPA证实为脑脊液吸收功能正常的阻塞性脑积水。手术方法为经侧脑室、室间孔、三脑室置入神经内镜，于三脑室底与脚间池造一瘘孔。结果术后随访半年-5年，39例有好转；10例因无改善于术后3个月再行脑室腹腔分流手术，术后脑脊液漏3例，未有出血、感染及神经功能损伤等并发症。结论脑室镜三脑室底脚间池造瘘适用于脑脊液吸收功能正常的阻塞性脑积水。脑脊液吸收功能判断需靠同位^99Tc^m-DTPA检查。继发性脑积水治疗效果好于原发性脑积水，大龄儿童效果好于婴幼儿。     

Whipple's disease with encephalopathy. A case report with review of the literature

A 58 year-old man developed a progressive encephalopathy four years after Whipple's disease onset with digestive, lymph node, and multiple joint lesions, treated over a period of two years. The diagnosis of neurological manifestations of Whipple's disease was based on clinical findings and the presence of PAS+ inclusion bodies in CSF cells. The outcome was fatal in spite of antibiotic therapy. Diagnostic features of this rare neurological affection are discussed. Preventive treatment and surveillance of patients with Whipple's disease are necessary even after well-conducted therapy.     

Hydrocephalus in craniosynostosis

Routine CT scanning in 221 patients with craniosynostosis revealed ventricular dilation in 40. In 5 hydrocephalus was obviously unrelated to the craniostenosis. The remaining 35 cases were associated almost exclusively with syndromic craniosynostosis. Ventricular dilation was mild in 22, moderate in 9, and marked in 4 patients. Clinical and radiological findings strongly suggest that three different mechanisms are involved in the pathogenesis of hydrocephalus: primary cerebral maldevelopment, brain atrophy, and CSF outflow obstruction. In the diagnosis of hydrostatic hydrocephalus with craniosynostosis, head circumference is no indicator of progressive hydrocephalus, and intracranial hypertension may be due either to CSF accumulation or to craniostenosis. The present study indicates that shunt treatment prior to correction of synostosis should be restricted to a few cases of rapidly progressing hydrocephalus. Secondary shunting of hydrocephalus may be considered if intracranial pressure remains high despite adequate cranial decompression. Shunting is not an appropriate treatment for craniostenosis — even in cases of concurrent ventricular dilation.     

神经内窥镜第三脑室底造瘘术治疗梗阻性脑积水

目的 探讨对梗阻性脑积水患者采用神经内窥镜下进行第三脑室底造瘘的手术方法．分析手术成功与失败的原因。方法梗阻性脑积水原因分别为第三脑室后部肿瘤5例，中脑顶板胶质瘤2例，Chiari畸形2例，另12例为不明原因引起的导水管梗阻或狭窄。同位素^99Tcm-TPA脑池显像显示为非脑脊液吸收障碍性阻塞性脑积水。神经内窥镜从侧脑室经蒙氏孔进入第三脑室，在乳头体前方第三脑室底最薄处造一瘘口与脚间池相通。结果术后随访12～26个月，所有患者脑积水症状均缓解，脑室体积缩小。结论神经内窥镜行第三脑室底造瘘治疗非脑脊液吸收障碍性脑积水是一种有效的微创手术。     

Neuropathologic analysis of 8 undiagnosed cases of cerebral cysticercosis

The presented material comprised 17 cases observed in four Warsaw hospitals in a period of 20 years. Nine patients with the pseudotumour syndrome were diagnosed correctly and referred to neurosurgical services. The remaining eight cases died in neurological hospital departments with the following clinical diagnoses: cerebral stroke 3, subarachnoid haemorrhage 1, comatose state preceded by dementia 1, chronic meningoencephalitis 1, status epilepticus 2 cases postmortem investigations demonstrated cerebral cysticercosis in all cases. In four patients with predominant symptoms of cerebrovascular disease lesions were found of the type of residual vasculitis cysticercosa, the sequelae of which might have caused secondary complications independent of concomitant arteriosclerosis. Dementia appeared in a patient with huge hydrocephalus consequent to numerous cysticerci. The patient with the diagnosis of meningoencephalitis had an inflammatory reaction of the ependyma and meninges caused by a cysticercus floating in the IV ventricle. Of the patients dying in status epilepticus attention is called to a 6-year-old girl with a solitary cysticercus localised subcortically in the motor area. The authors suggest that the possibility of cysticercosis should be kept in mind, despite its rarity, in cases with a not completely clear clinical manifestations of cerebrovascular disease, chronic meningoencephalitis and epilepsy or dementia.     

Whipple''s disease confined to the CNS presenting with multiple intracerebral mass lesions.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim. As CNS relapse of Whipple's disease may occur after several years, long term treatment should include antibiotics that are able to cross the blood-brain barrier.     

Dementia paralytica: deterioration from communicating hydrocephalus.

Five patients suffering from dementia paralytica who failed to improve or deteriorated after one or several high dosage courses of penicillin, had pneumoencephalographic patterns suggesting communicating hydrocephalus. Measurements of the ventricular index, ratio of cella media to width of the temporal horn, and the callosal angle differed from that in seven cases of dementia paralytica with associated cerebral atrophy. An isotope cisternogram in three cases with communicating hydrocephalus further confirmed a blockage of the cerebrospinal fluid (CSF) at the parasagittal subarachnoid space. Three patients exhibited the full syndrome of gait apraxia, incontinence, and pyramidal tract signs associated with a severe degree of dementia. Shunting of the CSF in three cases was followed by immediate improvement in two, one in a longlasting way. No active parenchymal inflammation was observed in any of three brain biopsy samples taken during surgery, except for leptomeningeal fibrosis in one. Chronic leptomeningitis in dementia paralytica may impair subarachnoid CSF absorption with subsequent communicating hydrocephalus. Progression or inadequate responses after therapeutic dose of penicillin in dementia paralytica should prompt investigation for this complication as an alternative, effective treatment could be offered.     

Intracranial pressure and ventricular expansion in hydrocephalus: have we been asking the wrong question?

The force that enlarges the cerebral ventricles and deforms the brain in hydrocephalus remains unclear. It is still widely thought to be elevated intraventricular pressure developing behind an obstruction to the flow of CSF. This view has led to the prediction that a large pressure difference should exist between the ventricles proximal to the obstruction and the subarachnoid space of the cerebral convexity distal to the obstruction. Yet measurements have shown consistently that such transmantle pressure differences are either small or absent. We propose a theory that reconciles the view that hydrocephalus is caused by obstruction to the flow of CSF with the observed absence of large pressure gradients across the cerebral mantle. Obstruction to CSF flow produces only a small pressure gradient — usually less than 1 mm Hg — that is sufficient to overcome the added resistance to flow and thereby to balance the absorption of CSF with its production. This mini-gradient is the effective force that initiates and sustains ventricular enlargement. It can coexist either with high or with normal intracranial pressure. The level of intracranial pressure is determined by the efficiency with which increments of ventricular pressure are transmitted through the parenchyma to the outer surface of the brain. In the presence of a rigid skull some transmission is required by basic laws of Newtonian mechanics. The efficiency of transmission depends primarily on the elastic properties of the brain. If the brain is relatively incompressible, transmission is efficient and high intracranial pressure is required to maintain the mini-gradient between the ventricles and the subarachnoid space, resulting in tension hydrocephalus. If the brain is more compressible, the parenchyma attenuates any increase of intraventricular pressure, reducing transmission to the outer surface. Intracranial pressure need not rise above normal levels to maintain the mini-gradient, leading to normal pressure hydrocephalus. The theory explains why tests measuring CSF resistance have limited diagnostic usefulness in hydrocephalus. It also predicts that very small stresses are sufficient to produce large deformations of the brain if these are allowed to occur slowly.     

Functional imaging of cerebrospinal fluid pathology

The most common problem addressed by dynamic radionuclide imaging of cerebrospinal fluid (CSF) abnormalities is differentiating patients with normal-pressure hydrocephalus (NPH) from those with other forms of degenerative brain disorder who would clearly not benefit from surgical treatment by ventricular shunting. Radionuclide cisternography (RC) SPECT and regional cerebral blood flow (rCBF) SPECT are critically important for the diagnosis and therapy management of patients with chronic hydrocephalus. However, radionuclide imaging is helpful not only in identifying patients with NPH showing improvement after shunting. RC reveals tracer activity outside the intracranial cavity, indeed. The importance of establishing the diagnosis arises from the fact that untreated leaks can be followed by meningitis in up to one quarter of patients. CSF collections may communicate with the subarachnoid space. RC SPECT has proved useful in assessing the communication of the arachnoid cysts (CSF collection) with the ventricular or subarachnoid compartment. Improved anatomical detail revealed by SPECT imaging is helpful in solving problems of the CSF pathology. Sensitive and accurate assessments of normal and disordered CSF dynamics can be obtained with RC SPECT.     

Natural course of intracranial pressure and drainage of CSF after recovery from subarachnoid hemorrhage

Twenty-eight patients were followed 12 months or longer after recovery from subarachnoid hemorrhage (SAH). The examination included spinal infusion test (SIT), clinical evaluation and cerebral computertomography (CT). The results indicate that when resting pressure and drainage of CSF are within normal limits 3 months after the hemorrhage there is little if any risk of developing late communicating hydrocephalus. In this study, most patients with a moderate impaired CSF drainage and/or slightly increased resting pressure 3 months after SAH did not show any increase in the ventricular size or clinical deterioration during the follow-up period. None of the 28 patients developed late communicating hydrocephalus or the clinical picture of normal pressure hydrocephalus.     

Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.

Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF). Blood flow measures were obtained using the microsphere injection method under controlled hemodynamic conditions in experimental CH (n=23) and surgical control (n=8) canines at baseline and at 2, 4, 8, 12, and 16 weeks. Cardiac output measures were made using the Swan-Ganz thermodilution method. Intracranial compliance (ICC) via cerebrospinal fluid (CSF) bolus removal and infusion, and oxygen delivery in CSF and prefrontal cortex (PFC) were also investigated. We observed an initial surgical effect relating to 30% CO reduction and approximately 50% decrease in CBF, MTP, and PBF in both groups 2 weeks postoperatively, which recovered in control animals but continued to decline further in CH animals at 16 weeks. Cerebral blood flow, which was positively correlated with CO (P=0.028), showed no significant relationship with either CSF volume or pressure. Decreased CBF correlated with oxygen deprivation in PFC (P=0.006). Cardiac output was inversely related with ventriculomegaly (P=0.019), but did not correlate with ICP. Decreased CO corresponded to increased ICC, as measured by CSF infusion (P=0.04). Our results suggest that CH may have more of an influence on CO and CBF in the chronic stage than in the early condition, which was dominated by surgical effect. The cause of this late deterioration of cardiac function in hydrocephalus is uncertain, but may reflect cardiac regulation secondary to physiologic response or brain injury. The relationship between cardiac function and CBF should be considered in the pathophysiology and clinical treatment of CH.