[Usefulness of SPECT and MRI in the diagnosis of atypical parkinsonism]. / Diagnostisk nytte av SPECT- og MR-undersøkelse ved atypisk parkinsonisme.

BACKGROUND: Clinico-pathological studies have shown that only three out of four patients with parkinsonism have idiopathic Parkinson's disease. In patients with so-called Parkinson plus syndrome, the degeneration in the brain is more widespread and the variety of neurological signs greater than in Parkinson's disease. The differentiation of these syndromes from Parkinson's disease can be difficult. Single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) can be of value in the differential diagnosis of parkinsonism. MATERIAL AND METHODS: We present three patients with atypical parkinsonism in whom MRI and SPECT with beta-CIT and epidepride was performed in addition to the clinical evaluation. RESULTS: The three patients all had a rapidly developing symmetric akinetic-rigid syndrome that responded poorly to levodopa. MRI showed findings regarded as typical for multiple system atrophy in two patients, but only nonspecific findings in the third patient. SPECT with beta-CIT showed a pronounced bilateral and relatively symmetric reduction in the striatal dopaminergic activity in all patients. SPECT with epidepride showed a clearly reduced striatal D2-receptor binding bilaterally in only one of the patients. INTERPRETATION: In patients with atypical parkinsonism, MRI and SPECT with beta-CIT and epidepride can give valuable support to the clinical diagnosis of a Parkinson plus syndrome.

Linkage analysis narrows the critical region for oculodentodigital dysplasia to chromosome 6q22-q23.

Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with high penetrance and variable expressivity. The anomalies of the craniofacial region, eyes, teeth, and limbs indicate abnormal morphogenesis during early fetal development. Neurologic abnormalities occur later in life and appear to be secondary to white matter degeneration and basal ganglia changes. In familial cases, the dysmorphic and/or neurodegenerative components of the phenotype can be more severe and/or present at a younger age in subsequent generations, suggesting genetic anticipation. These clinical features suggest that the ODDD gene is pleiotropic with important functions throughout pre- and postnatal development. We have performed two-point linkage analysis with seven ODDD families and 19 microsatellite markers on chromosome 6q spanning a genetic distance of approximately 11 cM in males and 20 cM in females. We have refined the location of the ODDD gene between DNA markers D6S266/D6S261 (centromeric) and D6S1639 (telomeric), an interval of 1.01 (male) to 2.87 (female) cM. The strongest linkage was to DNA marker D6S433 (Zmax = 8.96, thetamax = 0.001). Families show significant linkage to chromosome 6q22-q23 and no evidence for genetic heterogeneity.

Midbrain tremor and hypertrophic olivary degeneration after pontine hemorrhage.

A severe rest tremor arose in a patient's right arm 9 months after a pontine tegmental hemorrhage. Magnetic resonance studies at 4 and 10 months showed residual hemosiderin in the pons and increasing hypertrophic olivary degeneration (HOD) affecting primarily the left olive. The tremor was refractory to pharmacotherapy (clonazepam, propranolol, and levodopa), but was reduced after implantation of a thalamic stimulator device. Although pontine hemorrhage is among several common causes of HOD, it has not previously been appreciated as a cause of midbrain ("rubral") tremor. A disynaptic dentatorubroolivary tract associated with tremor and monosynaptic dentatoolivary tract associated with HOD may both be components of the rubroolivocerebellorubral loop implicated in midbrain tremor. Their proximity makes the combination of tremor and HOD after pontine tegmental damage plausible and even likely.

[Perimesencephalic subarachnoid hemorrhage]. / Perimesencefal subaraknoidalblødning.

Acute, non-traumatic subarachnoid haemorrhage is usually caused by a ruptured aneurysm. This is a serious condition involving high mortality. Perimesencephalic haemorrhage has recently been identified as a clinical subset of subarachnoid haemorrhage. A pattern of haemorrhage predominantly limited to perimesencephalic cisterns on CT is highly predictive of a normal angiogram, and is connected with an excellent prognosis. We describe two patients with perimesencephalic haemorrhage.

Assessment of the ophthalmic artery as a collateral to the cerebral circulation. A comparison of transorbital Doppler ultrasonography and regional cerebral blood flow measurements.

The role of the ophthalmic artery (OA) as a collateral to the cerebral circulation in carotid occlusive disease is somewhat controversial. The aim of this study was to assess the importance of this collateral by comparing the results of transorbital Doppler ultrasonography and regional cerebral blood flow measurements using SPECT and Xenon-133 inhalation in 41 patients with unilateral high-grade internal carotid artery occlusive disease. Both measurements were performed under basal conditions and after the intravenous administration of 1 g acetazolamide to test cerebral vasoreactivity. Based on the direction of OA flow, the patients could be divided into three groups. In Group 1 (n = 16) with anterograde OA flow before and after acetazolamide, baseline rCBF values did not differ significantly between the two sides, or from those of the controls. The side-to-side asymmetry of the response to acetazolamide was also normal. In Group 2 (n = 11) where the OA flow was anterograde or "0 flow" before, but became retrograde after acetazolamide, rCBF was significantly reduced on the symptomatic compared to the non-symptomatic side under basal conditions. However, the increase in rCBF after acetazolamide was within normal limits. In Group 3 (n = 14) the OA flow was reversed both under basal conditions and after the vasodilatory stimulus. Baseline rCBF was significantly lower (p < 0.05) on the symptomatic side compared to the non-symptomatic, and the asymmetry became even greater (p < 0.001) after acetazolamide. Our findings demonstrate that the OA may be an important collateral pathway in patients with ICA occlusive disease, and contribute to the cerebral perfusion reserve in the case of compromised blood supply.

Reduced Global Cerebral Blood Flow in Non-Demented HIV Positive Patients.

Twelve non-demented HIV positive men with different degrees of immunodeficiency were examined with single photon emission computed tomography (SPECT). Reduction in relative global cerebral blood flow was found in HIV positive patients compared to healthy HIV negative controls (p = 0.014). In the patients there was also a change in cerebral flow distribution, with lower global flow compared to central flow (p = 0.01), most pronounced in patients with early disease. In the patients with advanced HIV disease the relative cerebral blood flow was lower than in the controls in 108 of 116 (93%) regions investigated.

Cerebral vasoreactivity assessed with transcranial Doppler and regional cerebral blood flow measurements. Dose, serum concentration, and time course of the response to acetazolamide.

BACKGROUND AND PURPOSE: To improve the assessment of cerebral vasoreactivity using acetazolamide (ACZ), we studied the time course of the response and the relationship between dose, response, and serum concentration. METHODS: Blood flow velocities were measured with the use of transcranial Doppler ultrasonography in one of the middle cerebral arteries of 48 healthy subjects after the intravenous administration of 1 to 1.6 g ACZ. In 34 subjects (group 1), velocities were measured every second minute to detect the maximum middle cerebral artery velocity increase. We also measured regional cerebral blood flow using single-photon emission computed tomography in 27 of the subjects in group 1 before and approximately 15 to 20 minutes after the ACZ injection. The serum concentration of ACZ was measured in 15 subjects. In the remaining 14 subjects (group 2), middle cerebral artery velocity measurements were made 10, 25, 30, and 45 minutes after ACZ administration to obtain information regarding the late time course of the response. RESULTS: In group 1 the plateau phase of the velocity response was reached 8 to 15 minutes after ACZ administration. A large range of velocity increase was observed, and a significant correlation was found between the maximum velocity increase and the dose and serum concentration of ACZ. In group 2 subjects, maximum velocities were maintained 30 minutes after the injection, but after 45 minutes velocities had decreased to 68% of their highest level. No significant relationship was found between dose or serum concentration of ACZ and the regional cerebral blood flow increase. The velocity increase after ACZ was similar in both older and younger subjects. CONCLUSIONS: This study shows that cerebral vasoreactivity is best assessed 10 to 30 minutes after ACZ administration and that the dose should probably exceed 15 mg/kg if a maximum vasodilatory response in the cerebral circulation is to be obtained.

Doppler study of the ophthalmic artery in patients with carotid occlusive disease.

Assessing the adequacy of collateral circulatory pathways has become increasingly important in the investigation of cerebral circulation. Using transorbital Doppler ultrasonography (TOD), we examined the ophthalmic artery (OA) in patients with hemodynamic significant internal carotid artery (ICA) occlusive disease. The velocity and the direction of flow in the OA were studied in 45 patients (occlusion n = 27, stenosis > 75% n = 18), and in 30 age matched controls, under baseline conditions and within 30 minutes after the i.v. administration of 1 g acetazolamide as a vasodilatory stimulus. Based on the direction of flow before and after acetazolamide, the 45 patients could be separated into four groups with increasing degree of ICA lesions. In group I the OA flow was anterograde, but the velocity decreased after acetazolamide. In group II the OA direction became retrograde after acetazolamide, indicating collateral flow to the brain. In patients with retrograde OA flow following acetazolamide injection (group II-IV), the vessel reacted similarly to an intracranial artery, with marked increase in velocity when vasoreactivity was tested. TOD and the acetazolamide test provide useful information about potential collateral OA flow to the brain in patients with ICA occlusive disease.

Simultaneous assessment of vasoreactivity using transcranial Doppler ultrasound and cerebral blood flow in healthy subjects.

Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their perfusion territories were measured simultaneously in 36 healthy subjects. In 20 subjects, the measurements were first performed under basal conditions and then repeated 15-20 min after an intravenous injection of 1 g of acetazolamide. Reproducibility of simultaneous blood flow and velocity measurements was tested by examining 16 subjects on two occasions under basal conditions with an interval of 20 min. Relatively good reproducibility was found for repeated measurements of velocity and blood flow, being best when side-to-side asymmetry was assessed. The increase in blood flow velocities after acetazolamide was symmetrical (right side, 34.2%; and left side, 35.5%), and the velocity increase was significantly correlated with basal values. The increase in cerebral blood flow was also symmetrical (right side, 29.8%; left side, 30.1%) but not correlated with basal flow values. No significant relationship was found between velocity increase and increase in regional cerebral blood flow. This finding is probably not only due to methodological inaccuracies but may suggest that acetazolamide has an effect on the diameter of the middle cerebral artery or on the magnitude of this artery's perfusion territory. This study supports the use of acetazolamide for assessing cerebral vasoreactivity following the definition of lower limits for velocity and flow increase and for asymmetry of the response.

Ocular and cerebral blood flow measurements in healthy subjects. A comparison of blood flow velocity and dynamic tonometry measurements before and after acetazolamide.

The ocular and cerebral blood flow was studied in 15 healthy subjects using transcranial Doppler ultrasonography (2 MHz). The blood flow velocity in the precerebral carotid arteries, in the ophthalmic artery and in the middle cerebral artery was measured under baseline conditions and after i.v. administration of 1 g acetazolamide. To measure the intraocular pressure and the corneal indentation pulse amplitude, a dynamic tonometer was used. Pulsatile ocular blood volume was calculated from these values. After one single dose of acetazolamide a significant decrease in ophthalmic artery flow velocity, and a significant increase both in internal carotid and in middle cerebral artery velocity was found. A significant decrease in intraocular pressure and in pulsatile ocular volume after acetazolamide was also demonstrated. These findings suggest that the acute effect of acetazolamide may be associated with a reduced ocular blood flow, explaining some of the reduction in IOP.

Cerebral vasoreactivity in unilateral carotid artery disease. A comparison of blood flow velocity and regional cerebral blood flow measurements.

BACKGROUND AND PURPOSE: Hemodynamic information obtained by assessing cerebral vasoreactivity is of clinical interest and may have prognostic significance in patients with occlusive carotid disease. The aim of this study was to compare the results of transcranial Doppler and regional cerebral blood flow studies when used to assess cerebral vasoreactivity. METHODS: Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their respective perfusion territories were compared in 52 patients with severe unilateral carotid stenosis or occlusion. The studies were first performed under basal conditions and repeated after the intravenous administration of 1 g acetazolamide. RESULTS: Asymmetry (normal compared with pathological side) in middle cerebral artery blood velocity increase was significantly greater than the asymmetry in cerebral blood flow increase in the perfusion territories of the arteries. A significant correlation (r = .63, P < .0001) was found between asymmetry in percent velocity increase and asymmetry in absolute cerebral blood flow increase. The two methods agreed in their assessment of either a normal or a reduced vasoreactivity in 38 subjects and disagreed in 14. In six of the latter patients, who had no evidence of cerebral infarction, the asymmetry in velocity increase was abnormal, whereas asymmetry in flow increase was assessed as normal. CONCLUSIONS: We found a good correlation between the asymmetry in regional cerebral blood flow increase in the middle cerebral artery perfusion territories and asymmetry in the velocity increase in the middle cerebral arteries after administration of acetazolamide. These results suggest that transcranial Doppler examination combined with the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.

A comparison of regional cerebral blood flow and middle cerebral artery blood flow velocities: simultaneous measurements in healthy subjects.

Blood flow velocities were measured in both middle cerebral arteries (MCAs) of 36 healthy subjects using transcranial Doppler ultrasound. Measurements were first made using a hand-held probe. Velocities were then studied bilaterally with fixed probes under resting conditions and during simultaneous regional CBF (rCBF) measurements. A significant (p < 0.05) positive correlation was found between MCA flow velocities and rCBF in the estimated perfusion territory of this artery. The correlation coefficient was highest when the measurements were performed simultaneously (p < 0.001) or when velocities recorded with a hand-held probe were adjusted to take into account the significant velocity increase induced by the CBF study situation. The increased velocities during CBF measurements cannot be fully explained by the moderate but significant PCO2 increase. Other possible mechanisms are increased blood flow due to mental activation or MCA vasoconstriction secondary to stimulation of the sympathetic nervous system. The effect of mental activation and PCO2 differences should therefore be considered when comparing the results of repeated velocity and CBF measurements.

[Botulinum toxin treatment of spastic torticollis]. / Botulinumtoksinbehandling av spastisk torticollis.

Botulinum toxin A was administered to 19 patients with spasmodic torticollis. A significant decrease of abnormal head and neck movements was recorded, and all the patients who suffered pain reported relief. Side effects were minor and transient. The results of this study indicate that botulinum toxin is an effective means of treating torticollis.

Cerebral blood flow findings in moyamoya disease in adults.

Three adult patients with moyamoya disease are described. They presented with intracerebral hematoma, cerebral infarction and subarachnoid hemorrhage, respectively. Subarachnoid hemorrhage is rare in moyamoya and is usually the result of aneurysm rupture. No aneurysm was found in our patient. Regional cerebral blood flow (rCBF) and the cerebral perfusion reserve assessed by the acetazolamide test, were significantly reduced in all three patients. The areas with most reduced baseline rCBF and most impaired vasoreactivity did not always correspond to the site of the vascular accident, indicating that these CBF changes were at least in part due to the moyamoya disease and/or its underlying causes, and not solely to the vascular accidents.

Regional cerebral blood flow after long-term exposure to carbon disulfide.

Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43-65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide.

[Autoimmune optic neuritis]. / Autoimmun opticusneuritt.

We describe two patients with autoimmune optic neuritis. The initial symptom was severe loss of vision without clinical signs or symptoms of systemic autoimmune disease. The patients had recurrent attacks of optic neuritis in both eyes, causing permanent visual impairment despite conventional doses of corticosteroid. The only laboratory sign of autoimmune disease was a positive antinuclear antibody (ANA). These patients must be differentiated from cases with idiopathic optic neuritis or multiple sclerosis. Early diagnosis and high-dose corticosteroid therapy may be necessary, and may be successful in restoring visual function. Continued therapy with cytotoxic agents may be required.

A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity.

BACKGROUND AND PURPOSE: The aim of this study was to determine the ability of transcranial Doppler ultrasonography when used to assess cerebral vasoreactivity. The results of this method were compared with regional cerebral blood flow measurements. METHODS: Forty-three patients with symptoms suggesting cerebrovascular disease took part. Transcranial Doppler findings in the middle cerebral arteries were compared with regional cerebral blood flow in the corresponding perfusion territories before and after acetazolamide administration. RESULTS: There was a significant positive correlation between the absolute increase in cerebral blood flow in milliliters per 100 g per minute and the percent increase in velocity (r = 0.63). The right-left, side-to-side difference of the acetazolamide response obtained by the two methods also showed a positive correlation (r = 0.80). Control limits obtained from healthy subjects were used for both the blood flow increase (absolute values and asymmetry in absolute values) and the velocity increase (percent increase and asymmetry in percent increase). The two methods then agreed in their evaluation of vasoreactivity in 74 (86%) of the 86 middle cerebral artery perfusion territories; 20 (23%) were assessed by both methods as having a reduced vasodilatory reserve. Eleven hemispheres with a slightly reduced regional cerebral blood flow response to acetazolamide were not detected by transcranial Doppler, whereas all territories with a marked reduction were identified by Doppler. Only one hemisphere with a normal cerebral blood flow increase after acetazolamide administration was assessed by Doppler as having reduced vasoreactivity. CONCLUSIONS: Transcranial Doppler and the acetazolamide test may be used in clinical situations to assess cerebral vasoreactivity.

[Treatment of focal dystonia with botulinum toxin]. / Behandling av fokale dystonier med botulinumtoksin.

Focal dystonia and hemifacial spasms are difficult to treat. Medication and surgery may suppress the dystonic movements but the improvement is not satisfactory. The present article reviews use of Botulinum toxin in cases of focal dystonia. Injections of very small doses of Botulinum A toxin into the affected muscles is a new and efficient therapy for patients with focal dystonia. The toxin acts by inhibiting the release of acetylcholine from the nerve terminal, leading to a localized paralysis of the treated muscle. The effect is temporary and gradually diminishes, but the treatment can be repeated. The use of Botulinum toxin must be applied on the basis of a thorough knowledge of its effect and possible side effects.