Sciatica-like symptoms and the sacroiliac joint: clinical features and differential diagnosis.

PURPOSE: To compare the clinical features of patients with sacroiliac joint (SIJ)-related sciatica-like symptoms to those with sciatica from nerve root compression and to investigate the necessity to perform radiological imaging in patients with sciatica-like symptoms derived from the SIJ. METHODS: Patients with pain radiating below the buttocks with a duration of 4 weeks to 1 year were included. After physical and radiological examinations, a diagnosis of SI joint-related pain, pain due to disk herniation, or a combination of these two causes was made. RESULTS: Patients with SIJ-related leg pain (n = 77/186) were significantly more often female, had shorter statue, a shorter duration of symptoms, and had more often pain radiating to the groin and a history of a fall on the buttocks. Muscle weakness, corkscrew phenomenon, finger-floor distance ≥25 cm, lumbar scoliosis, positive Bragard or Kemp sign, and positive leg raising test were more often present when radiologic nerve root compression was present. Although these investigations may help, MRI of the spine is necessary to discriminate between the groups. CONCLUSIONS: Sciatica-like symptoms derived from the SIJ can clinically mimic a radiculopathy. We suggest to perform a thorough physical examination of the spine, SI joints, and hips with additional radiological tests to exclude other causes.

Treatment choices and patterns in migraine patients with and without a cardiovascular risk profile.

Treatment patterns in migraine patients with cardiovascular risk factors are largely unknown. A retrospective observational study was conducted to characterize the baseline cardiovascular risk profile of new users of specific abortive migraine drugs, and to investigate treatment choices and patterns in patients with and without a known cardiovascular risk profile. New users of a triptan, ergotamine or Migrafin (n = 36,839) from 1 January 1990 to 31 December 2006 were included. Approximately 90% of all new users did not have a clinically recognized cardiovascular risk profile. The percentage of new users with a cardiovascular risk profile did not differ between new users of a triptan, ergotamine or Migrafin and also did not change during the study period of 17 years. Differences in treatment choices and patterns between migraine patients with and without a known cardiovascular risk profile reveal a certain reticence in prescribing vasoconstrictive antimigraine drugs to patients at cardiovascular risk.

Secondary meningioma in a long-term survivor of atypical teratoid/rhabdoid tumour with a germline INI1 mutation.

OBJECTIVE: We report on a patient who developed a meningioma more than two decades after removal at a young age of an atypical teratoid/rhabdoid tumour (AT/RT), which was due to a germline INI1 mutation, and radio- and chemotherapy. MATERIALS AND METHODS: We present genetic evidence that the meningioma is not a recurrence or metastasis of the AT/RT and not due to the INI1 mutation, but is a radiation-induced tumour. CONCLUSION: This is the first case illustrating that improved survival of young patients with an AT/RT after aggressive treatment may be gained at the cost of an increased risk for the development of radiation-induced, non-INI1-related tumours.

Long-term survival and transmission of INI1-mutation via nonpenetrant males in a family with rhabdoid tumour predisposition syndrome.

Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by inheritance of a mutated INI1 gene for which only two multigeneration families have been reported. To further characterise the genotype and phenotype of RTPS, we present a third family in which at least three cousins developed an atypical teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed unusual long survival, and one of these developed an intracranial meningioma and a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the patients and in their unaffected fathers. This mutation prevents normal splicing and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma, was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of one of the patients carried an identical somatic rearrangement in the NF2 gene as the AT/RT, indicating that both tumours originated from a common precursor cell. In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma.

Thoracic radicular vessels by simultaneous intra-arterial and intravenous injection of araldite.

Spinal dural arteriovenous fistulas (SDAVF) consist of a shunt between a radicular artery and a radicular vein, resulting in a progressive paraparesis. They are most prevalent in middle-aged men (male to female ratio 5 to 1). It is unknown why the shunt develops. It is possible that there are anatomical differences between men and women, which may account for the sex difference in prevalence. We performed a study with simultaneous arterial and venous araldite injection in 5 male and 5 female human cadavers using different colors. The mean age of the human cadavers was 78 years (range 70-91). The human cadavers were not known to have suffered from spinal disease. We did not find significant differences in thoracic vasculature between men and women. Two different types of radicular arteries could be identified: The first was the arterial feeder of the root ganglion or the dura mater, which is also called the distal radicular artery. The second was the tributary of the anterior spinal artery, which is also called the medullary artery. We found three arteriovenous anastomoses between the radicular artery and the corresponding vein, and three between the radicular artery and venous plexus. We found a total of six thoracic arteriovenous shunts in four cadavers but their role in the pathogenesis of SDAVF remains uncertain. No vascular anatomic differences between men and women were found.

Distal myoclonus and late onset in a large Dutch family with myoclonus-dystonia.

We report a large myoclonus-dystonia (M-D) pedigree with a two-base pair deletion in Exon 5 of the epsilon-sarcoglycan gene. Three individuals had onset after age 40 years. Distal myoclonus of the arms was present in all 20 symptomatic mutation carriers. These findings expand the known phenotype of M-D and require revision of the current diagnostic criteria. Five of 14 asymptomatic mutation carriers who inherited the mutation from their mother showed minimal axial dystonia, arguing against a maternal imprinting mechanism.

Risk of ischemic complications related to the intensity of triptan and ergotamine use.

OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in specific overuse, is associated with the risk of ischemic complications. METHODS: We conducted a retrospective nested case-control study using data from the PHARMO Record Linkage System. All patients with more than one prescription for either a triptan or ergotamine were initially identified. Cases were all patients who were admitted to the hospital for an ischemic complication. Matched controls were assigned the same index date as the cases. The determinant was the intensity of use of triptans and ergotamine during 1 year preceding the index date. Overuse was defined as use of > or =90 defined daily doses during that year. Conditional logistic regression was used to estimate odds ratios (ORs), adjusting for confounders. Stratified analysis was used to estimate the risk for both patients using and those not using cardiovascular drugs. RESULTS: A total of 17,439 patients received more than one prescription. A total of 188 cases and 689 controls were identified. Triptan overuse was not associated with an increased risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of triptans in patients concomitantly using cardiovascular drugs did not increase this risk. Overuse of ergotamine turned out to be a risk factor for ischemic complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI 2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not increase the risk of ischemic complications. Overuse of ergotamine may increase the risk of these complications, especially in those simultaneously using cardiovascular drugs.

Spinal dural arteriovenous fistulas: a congestive myelopathy that initially mimics a peripheral nerve disorder.

Spinal dural arteriovenous fistula (SDAVF) is a rare and enigmatic disease entity. The clinical features and structural changes have been recognized since 1926, and the pathophysiology and the essentials of treatment since 1974, but up to the present day it is unknown why these fistulas develop. The fistula between a radicular artery and the corresponding radicular vein within the dural root sleeve leads to congestion of the venous outflow of the spinal cord and eventually ischaemia. Patients, who are mostly middle-aged men, develop a progressive myelopathy, which at the early stages of the disease often mimics a polyradiculopathy or anterior horn cell disorder. By the time involvement of upper motoneurons or sacral segments makes the diagnosis of SDAVF inescapable, patients suffer from considerable neurological deficits. The diagnosis relies on MRI, which shows swelling of the spinal cord, with a centrally located hyperintense signal on T2-weighted images, and with hypointense 'flow void' phenomena dorsal to the cord, representing enlarged and tortuous veins. Catheter angiography is required to determine the exact location of the fistula as well as the angio-architecture, on which the mode of treatment depends. If the arterial feeder of the fistula is a tributary of the anterior spinal artery, embolization is not possible. After embolization recanalization may occur, but this is rarely seen after filling of the draining vein with glue. Alternatively, operation is a safe and permanent mode of treatment. No prognostic factors have been reliably established. Muscle strength and gait disturbances respond better to treatment than pain and symptoms related to damage of sacral segments. In any middle aged male patient with ascending motor or sensory deficits in the legs, SDAVF should be considered in order to prevent irreversible handicap.

Stable incidence of childhood and adult glioma in The Netherlands, 1989-2003.

Time trends in the incidence of glioma may reflect changes in the prevalence of environmental risk factors for glioma. We therefore investigated trends in the incidence of childhood and adult glioma in The Netherlands from 1989 to 2003. We used population-based incidence data from the Netherlands Cancer Registry. We calculated European standardised incidence rates for glioma, and stratified for age, gender and glioma subgroups. Changes in the incidence were estimated by calculating the Estimated Annual Percentage Change. Similar to other countries, the overall incidence of glioma was fairly stable in The Netherlands during the period 1989 to 2003, for both children and adults. In adult astrocytic glioma, a significantly increasing incidence of high-grade astrocytoma was balanced by simultaneous decreases of low-grade astrocytoma, astrocytoma with unknown malignancy grade and glioma of uncertain histology. Most of these time trends can be explained by improving detection and diagnostic precision. Stable incidence rates of adult and childhood glioma suggest that no major changes in environmental risk factors have occurred, which influenced the incidence of glioma in the studied period.

Space-time clustering of glioma cannot be attributed to specific histological subgroups.

We previously showed that infectious exposures may be involved in the aetiology of adult glioma, by analysing for space-time clustering using population-based data from the South of the Netherlands. Here we extended these analyses and describe in detail the space-time clustering patterns in glioma subgroups, gender and age-categories. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. We used the spatial coordinates of the addresses at diagnosis in the analyses. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also analysed by a second order procedure based on K-functions. There was only statistically significant space-time clustering for oligodendroglioma. Clustering was present for adults aged 30-54 years and was more pronounced among males. Given the low prior probability of an infectious aetiology for this specific subgroup, these results should probably be interpreted as false-positive. We conclude that space-time clustering of glioma cannot be attributed to a specific glioma subgroup. The observed clustering in our previous study is therefore probably an overall effect within and between glioma subgroups.

The association between antihypertensive drugs and glioma.

We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case-control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03-2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal.

Right-to-left shunt and migraine: the strength of the relationship.

Several studies have shown that the prevalence of a cardial right-to-left shunt (RLS) in patients with migraine with aura is significantly higher than in patients without migraine. To assess the strength of the possible relationship between RLS and migraine, the literature concerning this subject was systematically reviewed. We identified seven relevant studies. Among patients with RLS migraine with aura was 3.5 times more prevalent than among subjects without RLS [Mantel-Haenszel odds ratio (ORMH) 3.5; 95% confidence interval (CI) 2.1, 5.8]. In patients with ischaemic stroke migraine was more than two times more prevalent in patients with RLS than in patients without RLS (ORMH 2.1; 95% CI 1.6, 2.9). Our review shows that there is a clear association between RLS and migraine, especially migraine with aura. The relationship between RLS and migraine is further substantiated by the observations of disappearance and improvement of migraine symptoms after closure of the foramen ovale. However, the mechanism as well as the question about causality of this association has to be further elucidated.

Spinal dural arteriovenous fistulas--an underdiagnosed disease. A review of patients admitted to the spinal unit of a rehabilitation center.

BACKGROUND: Spinal dural arteriovenous fistulas (SDAVF) are rare and present with non-specific symptoms. The diagnosis is difficult and it is therefore conceivable that patients may not be recognized. METHODS: We reviewed the intake forms of patients who had been admitted to the spinal cord injury ward of a rehabilitation center in the period 1980-2004 to identify possible patients with an undiagnosed SDAVF. Clinical and radiological data were evaluated in selected cases. RESULTS: In 20 of 1429 newly admitted patients to the rehabilitation center (in 614 of whom trauma was not the cause), we restudied the CT myelograms, MRI scans or spinal angiograms and in two of these we found an undiagnosed SDAVF, and one cerebral dural arteriovenous fistula. One of these three was diagnosed with SDAVF 8 years after the admission to the rehabilitation center; the other two patients had never been diagnosed with SDAVF. In 9 patients a diagnosis of SDAVF had already been established by the time they were admitted to the spinal cord unit. In 20 other patients the admission diagnosis was a vascular lesion or 'progressive myelopathy' but appropriate radiological studies had been destroyed or had never been performed. CONCLUSION: Our results suggest that spinal dural arteriovenous fistulas are an underdiagnosed condition.

Space-time clustering patterns of gliomas in The Netherlands suggest an infectious aetiology.

To test the hypothesis that infectious exposures may be involved in glioma aetiology, we have analysed space-time clustering and seasonal variation using population-based data from the South of The Netherlands between 1983 and 2001. Knox tests for space-time interactions between cases were applied, with spatial coordinates of the addresses at time of diagnosis, and with distance to the Nth nearest neighbour. Data were also analysed by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine seasonal variation of incidence. There was statistically significant space-time clustering in the Eastern, but not in the Western part of the region. Clustering was only present in adults, particularly in less densely populated areas. There was no evidence for seasonal variation. The results support a role for infectious exposures in glioma aetiology that may act preferentially in certain geographical areas.

[Gliomas: the role of environmental risk factors and genetic predisposition]. / Gliomen: de rol van omgevingsfactoren en genetische predispositie.

Exposure to ionising radiation is the only established risk factor for glioma. Although gliomas are looked upon as a non-heritable disease, physicians regularly see patients with affected relatives in practice. A few monogenetic tumour syndromes explain < 5% of all gliomas: neurofibromatosis type 1 and 2, Li-Fraumeni syndrome, tuberous sclerosis, Turcot syndrome, Gorlin syndrome, and the melanomaastrocytoma syndrome. Aggregation ofgliomas in families without these tumour syndromes also occurs. The overall familial pattern is generally atypical for hereditary cancers. Relatives are estimated to have a 2- to 9-fold increased risk. The occurrence ofgliomas in families can probably best be explained by a multifactorial model: environmental risk factors with a genetically determined susceptibility for these risk factors. The identity of the genetic variants leading to this predisposition remains to be determined. When there are indications of a hereditary tumour syndrome, additional diagnostic investigation is indicated.

[Posture-dependent headache due to the spontaneous hypotension syndrome]. / Houdingsafhankelijke hoofdpijn door het spontane liquorhypotensiesyndroom.

A 40-year-old woman and a 47-year-old man presented with acute posture-dependent headache. A spontaneous intracranial hypotension syndrome was diagnosed in both cases. MRI with a gadolinium contrast medium revealed staining of the pachymeninges. In the woman, cisternography revealed leakage of spinal fluid at the level of the cauda equina. Neither an infusion of caffeine nor an epidural blood patch helped, but the symptoms disappeared spontaneously. In the man, cisternography indicated leakage at the level of the 3rd thoracic vertebra. The symptoms disappeared rapidly after treatment with a local blood patch. Posture-dependent headache is typical for the intracranial hypotension syndrome. The headache is usually relieved by lying down and aggravated by standing up, but the reverse has also been reported. This headache can develop in a short time, sometimes acutely, and may persist continuously. The syndrome is usually caused by leakage of cerebrospinal fluid due to rupture of the dura mater, which may occur spontaneously. The diagnosis can be established by gadolinium MRI, revealing a striking pattern of diffuse pachymeningeal enhancement. Subdural fluid accumulations may also be seen. Indium-pentetreotide cisternography can often localise the spinal fluid leak. Intravenous caffeine and the application of an autologous epidural blood patch are possible treatment options, but spontaneous recovery may also occur.

[The opsoclonus-myoclonus syndrome]. / Opsoclonus-myoclonussyndroom.

The opsoclonus-myoclonus syndrome (OMS) was diagnosed in nine patients, two men and seven women, varying in age from 34 to 65 years. In two cases the findings indicated a post-infectious form, in three cases there was a malignancy, in one case there was a connection with the use of medication and in three cases the cause was unknown. OMS is a rare neurological disorder with symptoms of rapid, involuntary saccadic eye movements (opsoclonus) and sudden involuntary muscle contractions (myoclonus). It has been associated with infections, malignancies, intoxications and metabolic disorders. In 50% of the cases no cause can be identified. There is evidence for dysfunction ofbrainstem and cerebellar pathways and in many cases an (auto-)immune process is implied. Once the diagnosis has been established, screening for occult malignancy is indicated. The prognosis of idiopathic and post-infectious OMS is generally good and the treatment is mainly supportive.

Hypertension as a risk factor for glioma? Evidence from a population-based study of comorbidity in glioma patients.

BACKGROUND: Little is known about the aetiology of glioma. Research is often hampered by the low incidence and high mortality of the disease. Concomitant diseases in glioma patients may indicate possible aetiological pathways. We therefore studied comorbidity in glioma patients. PATIENTS AND METHODS: We performed a case-control study using population-based data from the Eindhoven Cancer Registry. We compared prevalences of concomitant diseases in 510 glioma patients with two reference cancer populations from the same registry. RESULTS: Compared with all other cancer patients, a significantly higher prevalence of hypertension was found in glioma patients for age categories 60-74 years [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.02-1.84] and 75+ years (OR 2.37; 95% CI 1.34-4.21). The association was most pronounced in elderly men and in astrocytic glioma, with a maximum in age category 75+ years (OR 5.86; 95% CI 2.20-15.7). The prevalence of cerebrovascular disease was higher in glioma patients >45 years old (OR 1.67; 95% CI 1.12-2.47), whereas the prevalence of other cancers was lower (OR 0.64; 95% CI 0.48-0.87). No consistent associations were detected for several other concomitant diseases. CONCLUSIONS: Our data suggest an association between hypertension and glioma, although questions remain about causality and the possible mechanisms. We hypothesise that this association is mediated through potentially neurocarcinogenic effects of antihypertensive medication.

Type I cerebral dural arteriovenous fistulas of the lateral sinus: clinical features in 24 patients.

To review the clinical and diagnostic characteristics of type I cerebral dural arteriovenous fistulas (CDAVF) of the lateral sinus medical records of 24 patients with Type I CDAVF were retrospectively reviewed. All patients were interviewed aiming at presenting symptoms, impact on daily functioning, diagnostic delay, relevant medical history and post-treatment status. Nineteen of 24 patients (79%) were women. The median age at the time of diagnosis was 56 years (range 32-69). Unilateral pulsatile tinnitus was the presenting symptom in all patients. A bruit could be heard at auscultation on the retroauricular skull in all patients. The median diagnostic delay was 17.9 months (range 1-120). Standardized magnetic resonance imaging (MRI) of the brain was normal in all patients. The diagnosis of CDAVF was confirmed on cerebral angiography. In conclusion, CDAVF type I of the lateral sinus occurs predominantly in middle aged women and presents with unilateral pulsatile tinnitus, which resulted in impairment of social and occupational functioning in the vast majority of patients. An audible bruit at retroauricular auscultation confirms the clinical diagnosis of a cerebral dural fistula. MRI is not helpful in the diagnosis and cerebral angiography is indicated to classify the dural fistula.

Spinal dural arteriovenous fistulas are not associated with prothrombotic factors.

BACKGROUND AND PURPOSE: The cause of spinal dural arteriovenous fistulas (SDAVF) is unknown. In intracranial dural arteriovenous fistulas, an association with factor V Leiden mutation has been found. Therefore, we studied the association between prothrombotic factors and SDAVF. METHODS: Factor V Leiden mutation, factor II mutation, protein S, protein C, factor VIII, von Willebrand factor, antithrombin III, and lupus anticoagulant were determined by means of standard laboratory tests in 40 patients and 119 control subjects matched for sex and age. RESULTS: Factor V Leiden mutation was not found in the patient group and was found twice in the control group. Factor II mutation was found in 1 patient and in none of the control subjects. There was no decreased activity of protein S, protein C, factor VIII, von Willebrand factor, or antithrombin III in patients in comparison with controls. Lupus anticoagulant was not found in the patient group and once in the control subjects. CONCLUSIONS: We conclude that it is unlikely that prothrombotic factors are involved in the pathogenesis of spinal dural arteriovenous fistulas, but subtle associations are not ruled out.