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STROKE (CEREBROVASCULAR ACCIDENT)

CT scan shows massive stroke - (Source)
stroke

TABLE OF CONTENTS

I. PATHOLOGY

II. DBS APPLICATION

III. OTHER TREATMENTS

IV. THERAPY ANALYSIS

V. SUCCESSES AND ADVERSE EVENTS

VI. MAJOR RESEARCH CENTERS

 

PATHOLOGY

A stroke occurs when a blood clot either blocks an artery or a blood vessel, altering the flow of blood to the brain. As a result brain cells begin to die and brain damage proceeds. When the brain cells of a certain region die the abilities of that area are adversely affected and can even be lost. Implications of a stroke can include a loss of speech, movement, and memory.

 

The extent and kind of damage caused by a stroke is determined by the area of the brain affected and the amount of brain tissue that dies. While some patients experience a full recovery, over 2/3 will face some sort of disability.

 

Ischemic stroke - (Source)
stroke2

Risk factors that increase one’s chance of a stroke include high blood pressure, which can weaken blood vessels and damage the brain, atrial fibrillation, which enables blood to pool in the heart and create possible clots, high cholesterol, which can clog the arteries,  and diabetes (patients face comorbidities that increase the chance of stroke). Lifestyle choices that can also increase stroke risk include tobacco use or smoking since blood vessels are damaged, alcohol use, and obesity since the body’s circulatory system is placed under greater stress. Uncontrollable risk factors include age, each decade after age 55 one’s chance for stroke doubles, gender – men are more prone to stroke but strokes are more lethal for women, race – African Americans, Hispanics, and Asian/Pacific Islanders have a higher risk of stroke than Caucasians, family history, and previous history of stroke.

 

The symptoms of a stroke include sudden numbness of weakness of the face, arm, or leg, sudden confusion, difficulty speaking or understanding, an inability to see out of one or both eyes, difficulty walking, dizziness, imbalance, and a severe headache with unknown cause.

 

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DBS APPLICATION

DBS for the purpose of stroke recovery or improvement of symptoms is not FDA approved. There have been a few clinical studies conducted that investigate the effects of DBS on stroke patients.  However many of these studies consist of small numbers of patients and the method of assessing post surgical pain has been the use of a visual analogue scale and the McGill’s pain questionnaire, which provides a great deal of patient subjectivity.

 

The areas of the brain stimulated for the purpose of alleviating the symptoms associate with stroke include the periventricular gray area (PVG), the sensory thalamus (Ventroposterolateral nucleus-VPL) or both.

 

In a 2000 publication by Phillips et al. a deep brain stimulator was implanted in a 48 year old man who had been experiencing pain and a paretic arm as a result of a stroke. The electrode was placed in the periventricular grey matter of the third ventricle. Following electrode stimulation the patient noted an improvement in the voluntary movement of his paretic arm and leg, including conducting movements he could only do prior to the stroke. Five months post-surgery the patient reported a loss of the surgical benefits, it was noted that the electrode had migrated from the target site; however, after reinsertion the health benefits were restored. The patient also noted that the leg and arm pain experience was exacerbated during times of sustained physical activity and could not be relieved by DBS.

 

DBS has also been studied in relation to central post stroke pain, which affects approximately 2-8% of patients after a stroke. Central post stroke pain is generally resistant to pharmaceuticals and remains very unpleasant for patients. In a 2002 publication by Nandi et al. four patients with stroke neuropathic pain had DBS; electrodes were placed in the ventroposterolateral thalamic nucleus and peri-ventricular grey area contralateral to the site of pain.

 

In a clinical study conducted in the UK by Owen et. al, DBS was studied in 15 patients who suffered from intractable neuropathic pain following a stroke.  Most of the patients had two electrodes (Medtronic 3387) placed inside the brain, one for the PVG and another for the VPL; those who had suffered strokes in the sensory thalamus were only implanted in the PVG/PAG. For the first week post-surgery the electrodes were external to allow for trial stimulation, each of the electrodes was tried individually and together  to assess the area of pain and to achieve maximum pain relief. Three of the fifteen patients did not feel as if there was a notable enough improvement to go to full implantation of the pacemaker. The 12 remaining participants had the entire Medtronic Synergy Pacemaker implanted. At a two year follow-up, nine patients noted a preference for chronic stimulation of the PVG, one of the VPL, and two preferred the activation of both electrodes. Data also suggested that there was a greater reduction of pain for those in the cortical stroke group than the subcortical stroke group. In addition, seven of the 12 patients stopped all analgesics and five patients altered their regimen to “as required.”

 

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OTHER TREATMENTS

Strokes are often treated with thrombolytics, drugs that dissolve the clots and reestablish the flow of blood to the brain. Treatment is most effective when thrombolytic therapy is given immediately.

 

Activase (Alteplase recombinant) was marketed in 1996 and was the first acute ischemic stroke treatment approved by the FDA. In a five-year trial conducted by the National institute of Neurological Disorders and Stroke it was found that patients carefully selected to receive Activase within three hours of experiencing stroke symptoms showed a 33% advantage in recovery without disability after three months in comparison patients receiving a placebo. Side effects of Activase include brain hemorrhage.

t-PA drip - (Source)
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Tissue plasminogen activator or t-PA can be used in IVs to help dissolve a clot, by converting or activating plasminogen to dissolve a blood clot. Studied of t-PA have indicated that there is no increase in death rate compared to patients receiving a placebo.

 

In 2007 MERCI (Mechanical Embolus Retrieval in Cerebral Ischemia) was approved as a mechanical alternative to t-PA. A flexible memory wire is placed through the groin up into the blocked artery where a coiled wire grabs the clot and pulls it into a catheter.

 

In early 2008 the Penumbra System was approved for the safe revascularization of occluded vessels resulting from an ischemic stroke. The system restores blood flow by suctioning blood clots in the brain and greatly expands the timeframe by which doctors can intervene due to an acute ischemic stroke.

 

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THERAPY ANALYSIS

DBS differs from most of the current emergency therapies used to treat strokes. Instead of trying to remove a clot, DBS is intended to relieve the after effects and symptoms caused by stroke, including pain and motor effects. Currently Post-stroke patients are prescribed rehabilitation, which includes physical therapy and speech-language pathology. Such therapies provide varying degrees of success depending on the degree of damage to the patient’s brain and the area that the stroke affected.

 

Although motor cortex stimulation has been experimentally used as a method to relieve intractable neuropathic pain post-stroke, the literature provides extremely variable results.

 

In the studies of DBS in response to pain associated with stroke there is a promising amount of literature suggesting that patients do experience an alleviation of the pain experienced prior to stimulation. Although the studies regarding DBS and stroke have been relatively small, the majority of patients have reported a reduction in pain, which is more conclusive than the results of rehabilitation, which is limited to the area of the brain damaged and the ability of the patient to overcome the often debilitating pain associated with strokes.

 

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SUCCESSES AND ADVERSE EVENTS

Scientific consensus seems to be that a substitution of pain with a sensation of warmth in the area of pain is considered a success.

 

In the aforementioned 2002, Nandi et al. publication and study one of the four patients developed a CSF leak after the implantation of the electrode in the PVG and later suffered from a hematoma related to the surgery and in another patient the trial stimulation didn’t provide any pain relief. Three of the four patients perceived a relief in pain; two of the patients in the study noted a +40% relief in pain and the third patient experienced a reduction in pain but chose not to proceed with full implantation.

 

Complications noted in the Owen et al. study include one patient fracturing the extension lead after hitting his head; however, this was corrected via surgery and pain relief was restored. Another side effect was “eye bobbing” that occurred when the lowest part of the PVG was stimulated at high voltages.

 

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MAJOR RESEARCH CENTERS

The majority of studies conducted to treat stroke patients with DBS have occurred in the UK.

University of Leeds - in association with Leeds General Infirmary, Leeds, UK

Oxford University - in association with Radcliffe Infirmary

 

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