Pre and post betahistine therapy 99m Tc - HMPAO brain spect studies in patients with vertigo.
Vertebro basilar insufficiency (VBI) is a well known cause of vertigo. Brain Single Photon Emission Computed Tomography (SPECT) is an important diagnostic tool to detect and to quantitate the perfusion abnormalities in different areas of the brain. Effect of an antivertigo drug Betahistine on improving the hypoperfusion in different areas of the brain in vertigo patients was studied using brain SPECT. Betahistine at a dose of 16 mg three times daily was shown to improve perfusion in the hypoperfused areas of the brain resulting in relief from symptoms of vertigo. The cerebellar region, which is the most important area involved in vertigo patients with vascular pathology, showed almost complete normalisation of perfusion following Betahistine therapy.
Vertigo is a clinical dilemma with many causes. Vertebro basilar insufficiency (VBI) is a well known cause of vertigo with or without accompanying neurological symptoms. Diagnosis of vascular aetiology of vertigo is important and should be done at an early stage so that drug therapy or surgery using modern techniques could be instituted to alleviate vertigo. This would prevent brain damage secondary to cerebral ischaemia. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) are the preferred modern investigative procedures for the diagnosis of cerebrovascular diseases. SPECT is another modern investigative procedure which detects ischaemic areas much early in the course of the disease, before the structural changes appear on MRI.
Betahistine is a widely used drug for the management of vertigo. Various studies have shown that betahistine improves cochlear microcirculation and also increases the cerebral blood flow. It has also been shown that betahistine reduces firing activity of lateral vestibular nucleus neurons.
The present study was undertaken in patients with vertigo with the following objectives. i) To detect and quantitate the perfusion
i) abnormalities in different areas of brain.
ii) To assess the response of an antivertigo drug betahistine on the perfusion abnormalities of the brain in patients with vertigo.
Patients presenting with the main symptom of vertigo in the neurology clinic were included in the study. Associated symptoms like tinnitus, hearing loss, nausea or vomiting, if reported by patients, were also noted. All these patients underwent complete neurotological examination, including audiometry and electronystagmography. Patients with no peripheral cause of vertigo and with a probable diagnosis of ischaemia of vertebro basilar system were included in the study.
These patients were subjected to baseline isotope perfusion brain scan - 99m Tc - HMPAO brain SPECT study for confirmation of the diagnosis. The technique involved administration of 15 millicurie of 99m - Tc HMPAO intravenously, followed by brain images in 360 degrees in 64 views. The images were reconstructed to obtain transaxial, coronal and sagittal slices of 6 mm thickness. The areas showing reduced uptake were referred to as ischaemic or hypoperfused areas. The perfusion defect was quantified in percentage based on a colour scale. A 20 colour scale was used. Left to right comparison was done in all the patients. The patients showing hypoperfusion at baseline were studied further.
All patients who demonstrated perfusion abnormalities in baseline SPECT images were treated with betahistine 16 mg three times daily (Vertin 8 mg tablets, 2 tablets three times daily) for a maximum treatment period of 6 weeks or earlier, until remission of vertigo attacks. The clinical examination was repeated every week. Patients were questioned on the overall relief from symptom of vertigo, using a rating scale of complete improvement, moderate improvement, and no improvement. The improvement of associated symptoms was also observed. The clinical findings were correlated by repeated SPECT study. The above imaging procedure with 99 m - Tc HMPAO was repeated after betahistine treatment for post therapy images. The improvement in these hypoperfused areas from baseline was quantified as percentage and also assessed visually. More than 15 % improvement in perfusion was taken as significant improvement.
Eleven patients of vertigo comprised 7 female and 4 male patients. Average age of the patients was 58.6 years. The duration of vertigo ranged from 1 month to 10 years. Neurotologic examination showed no peripheral cause of vertigo in any patient.
SPECT study of these 11 patients at baseline revealed no perfusion abnormality in 2 patients. Nine patients showed evidence of ischaemia on baseline study. Two patients were lost to follow-up [Table I]. Seven patients completed the study and could be followed up for repeat SPECT images after betahistine therapy. Out of 7, six patients showed significant improvement in perfusion after betahistine therapy. One patient showed partial improvement in perfusion. [Table II]
The regional distribution of perfusion abnormalities in these 7 patients at baseline is given in [Table III]. There were 18 abnormal areas of which 4 were in cerebellar, 9 in temporal and 5 in parieto-occipital regions. After betahistine therapy, there was complete normalisation of perfusion in all cerebellar areas. Seven out of 9 temporal areas improved while 3 out of 5 parietooccipital areas showed improvement in perfusion [Figure. 1-3] .
The SPECT results matched with the clinical findings, patients' own assessment and investigators' assessment. Six patients expressed complete relief from vertigo attacks. One patient indicated that attacks were milder and less frequent, indicating partial improvement. Thus there was a good correlation between the clinical findings and the SPECT studies. The associated symptoms such as nausea, vomiting and tinnitus improved with betahistine therapy.
No untoward side effects like drowsiness and gastrointestinal disturbances were reported by any patient.
The diagnosis of vertebro-basilar insufficiency due to ischaemia is very important in the management of vertigo. There is a need for a screening test, which would give the diagnosis with a high sensitivity instead of performing expensive investigations like the MRI, MRA or invasive procedures like carotid angiography.
The brain perfusion scan with 99Tc - HMPAO is one of the simplest techniques to perform, which could indicate the perfusion in different areas of the brain. In this technique, an isotope coupled to an oxime compound (HMPAO) is injected intravenously. It then localises in the brain substance in direct proportion to the blood flow in each area of the brain.
In other words, the image could be a direct demonstration of the quantity of blood flow in each area of the brain. Thirty minutes after the administration of the tracer, brain perfusion images are acquired in 360o in 64 views. Images are reconstructed by the computer to obtain brain perfusion images in transaxial, coronal and sagittal slices of 6 mm thickness. The computer software also enables to quantify the amount of blood flow in each area of the brain. Thus the imaging technique not only permits visual analysis but also provides means to quantify the blood flow in each area of the brain.
The technique is currently used in transient ischaemic attacks (TIAs), epilepsy and post cerebral infarction to assess the cerebro vascular reserve in the area of the damaged brain. It is also used to differentiate Alzheimer's dementia from multi infarct dementia and pseudodementia.
In our study, we assessed the role of 99m Tc- HMPAO brain SPECT in diagnosing the ischaemia in the vertebro basilar region which could be responsible for vertigo. We also used the same technique in assessing the therapeutic benefits following betahistine therapy. The improvement in perfusion following betahistine therapy was assessed visually as well as quantitatively. There was thus a documentary proof of the effect of the drug in patients with ischaemia of vertebro basilar region.
The cerebellar region is one of the most important areas involved in vertigo with vascular pathology. All cerebellar areas showed complete normalisation of perfusion with betahistine therapy. Overall, 6 out of 7 patients showed improvement in perfusion following betahistine therapy. Remaining one patient showed partial improvement in perfusion. In the patient with partial improvement, if the treatment had been continued for a longer period, it could have possibly offered better results. This study, being preliminary, was carried out as an open trial. An interesting research area in future will be to carry out a placebocontrolled and double blind study in this field.
The antivertigo drug betahistine is H1 receptor agonist and H3 receptor antagonist, It is well studied in various clinical trials for vertigo. Vascular effects of the drug are reported both in cochlea and brain. Suga and Snow studied the effects of the drug in the cochlea and demonstrated that betahistine caused marked and sustained improvement of cochlear blood flow without affecting systemic blood pressure. Rivera et al showed that betahistine caused improvement of cerebral blood flow in patients with vertebro basilar insufficiency. Unemoto concluded that betahistine causes dose dependent inhibition of spike generation of lateral vestibular nuclei firing. Its efficacy in controlling vertigo attacks is well studied in various clinical trials., Betahistine is shown to exhibit dose-dependent effect. Oosterveld studied the effects of various doses (8, 16 and 32 mg) of betahistine on induced vestibular nystagmus in a double-blind study in 10 normal subjects. The study showed that betahistine reduced the duration of induced nystagmus in a dose-dependent manner. Betahistine, being non-sedative, does not hamper the vestibular compensation process in vertigo patients.
99m Tc HMPAO brain SPECT is an important diagnostic test to confirm the vascular cause of vertigo and to quantitate the hypoperfusion in different areas of brain. It is a valuable tool to quantitate the vascular effects of drug. Betahistine in a dose of 16 mg three times daily is an effective antivertigo therapy, which improves blood perfusion to ischaemic areas of the brain. Ischaemia of cerebellar region, which is the main cause of vertigo, showed complete normalisation of perfusion with betahistine therapy.