We report seven patients who presented with clinical manifestations of ischemic cerebrovascular disease (CVD), dementia, and on CT Scan radiological signs of active neurocysticercosis and Binswanger’s Disease (BD) were found. Two patients died due to bilateral pulmonary thromboembolism secondary to deep venous thrombosis on lower limbs and the others remain alive. In almost all of them after one day of treatment with praziquantel(PZQ) some aggravation of the clinical manifestations of BD were observed. We have hypothesized about the Taenia solium-microglial activation-coagulation disorder and glial disorders-Blood-Brain-Barrier disturbances-Binswanger’s disease. We considered that anti-parasitic therapy for active NCC in patients with an associated BD should be prescribed for some isolated cases when it’s extremely necessary.
Key Notes: Vascular Dementia, Binswanger’s disease, Neurocysticercosis, Praziquantel
In 1550, neurocysticercosis (NCC) is described for the first time when Parandi found some rounded vesicles filled of cerebrospinal fluid (CSF) on the corpus callosum in a patient with cerebovascular disease (CVD). In 1558 Kumber provided a more detailed description of NCC from the autopsy of epileptic patient and Malpigh in 1686 nominated its as a parasitic disease and identified the parasites into the intracerebral vesicles which were named cysticercus by Laennec in XIX century.1 NCC is the most common parasitic infection of the brain caused by the larval stage (cysticercus cellulosae) of the pig tapeworm Taenia solium, affecting more than 50 million of peoples all over the world. NCC is characterized by epilepsy, intracranial hypertension, neuropsychiatry manifestation, dermatological and ocular problems, more detailed information about NCC in our region are available on-line.2 3 4 5
In 1672, the English physician Thomas Willis (1621-1672) provides the first accurate clinical observations of patients with post-stroke vascular dementia. Willis said: " I have observed in many cases that when, the Brain being indisposed, they have been distemper’d with a dullness of mind and forgetfulness, and then afterwards with a stupidity and foolishness, they would afterwards have fallen into a Palsie, which I oft did predict. For according as the places obstructed are more or less large so either a universal Palsies, or an half Palsie of one side, or else some partial resolutions of members happen".6
In 1938, Dechambre described lacunes for the first time while worked under Cruveilhier supervision at the Salpétriére Hospital in France. The word lacune (French lacune from the Latin lacuna, ae, a tiny hole, pit, or cavity) denotes a small, cystic cavity of the brain substance that usually results from an ischemic infarction in the territory of a penetrating arteriole; lacunes may follow very rarely small deep hemorrhages or an isolated giant dilation of the perivascular space.6
In 1894, Alzheimer and Binswanger described "arteriosclerotic brain atrophy", a condition characterized by "military apoplexies" or "disease foci" (lacunar infarcts) affecting the basal ganglia, internal capsule, and white matter (WM) of the Centrum ovale, associated with severe arteriosclerosis of small and large vessels.6 he also described an associated enlarged ventricles and normal cerebral cortex, Binswanger separated its from neurosyphillis and other forms of dementia in elderly peoples.7
The term état criblé (Cribiform state) and leukoaraiosis (LA) described in 1842 and 1987 respectively refers to the dilations of perivascular spaces around cerebral arterioles in the brain of elderly peoples and the radiological images of loss of density of the periventricular WM observed by computerized tomography (CT) of the brain accordingly.
In some textbook of neurology, Binswanger’s disease (BD) is described as a very uncommon disorder characterized by pseudobulbar palsy with vascular dementia due to lesions on the WM, and LA is seen on the CT Scan or MRI in third age’s patients (sixth or seventh decade). To the knowledge of those authors, about 150 cases had been reported,7
The attenuation of the subcortical WM (LA) is a hallmark of the BD. When this syndrome was described by Binswanger, he identified it as a different form of dementia (encephalitis subcorticalis chronica) with lesions of the subcortical WM "severe atheromatosis of the arteries." In 1982 Tomonaga8 reported an incidence of BD between 3 to 12 percent in the elderly. The etiology of BD is still not certain but dysfunction of the blood-brain-barrier seems to be always present.
Some of the pathological hallmark (WM lesions) of BD are also present in NCC. We had have been investigating patients with NCC and associated ischemic CVD, but unfortunately these results are still in process, however lesions of the WM in ischemic stroke does not differ from lesions on the WM in BD (WM lesions plus lacunes) although that lesions are more diffuse and prominent in BD.9
The aim of this study is to report our results from a group of patients fulfilling diagnostic criteria for BD10 (dementia-based on Mini-Mental-State, and bilateral radiological abnormalities on computed tomography), evidence of systemic vascular disease, manifestation of focal cerebrovascular disease or evidence of "subcortical" cerebral dysfunction, and NCC (Evidence of cystic lesions showing the scolex on CT)11. All of them were treated with PZQ (100 mg/kg) and prednisone (30 mg/day).
MATERIAL AND METHODS.
Seven patients diagnosed as BD and NCC were identified prospectively for the study among other patients referred to neurology clinic in Umtata General Hospital during five years period. Some of those patients presented with an associated pulmonary tuberculosis (PTB) and all of them with long-standing history of arterial hypertension. Hypertension was diagnosed according to the criteria of the World Health Organization (Geneva, Switzerland; 1985. Technical Report Series 727). Our hospital is a tertiary-care institution that offers neurological services for a rural area of about 6, 4 million peoples. Patients with stroke (defined as focal neurological deficits of acute onset, lasting more than 24 hours, due to brain ischemia as shown by CT Scan or after clinical and neuroradiological workup) were admitted to our Stroke Units (female and male) after examination in the emergency and casualty department, without further selection. Those patients were studied according to the following protocol: Detailed history of the present complaint, identification of the risk factors for stroke, and physical examination, neurological evaluation at entry and daily for the first ten days, laboratory tests, chest x-ray, electrocardiogram and hemodinamic tests, CT Scan of the brain, coagulation screen, lipid profile, and others looking for cardiovascular diseases or peripheral vasculopathies were carried out when necessary.
After the CT scan of the brain, eligible patients (n=7) had an active form of NCC without clinical signs of raised intracranial pressure.
Exclusion criteria for anti-parasitic treatment in this group included age < 59 or > 81 years, resolution of deficits within 24 hours, normal CT Scan, history of alcohol abuse (ie, > 600 g/wk), history of retarded psychomotor development, psychosis, other CNS disorder or systemic diseases known to involve the CNS, patients with severe aphasia and/or sensory impairment (blindness, deafness), severe depression and finally high suspicion of tuberculomas, pyogenic brain abscesses, mycotic granulomas, and primary or metastatic brain tumors (See the flow chart). Apart from aspirin and anticoagulant (when it was necessary), steroids medications and antiparasite treatment, other concomitant treatment was prohibited for patient while participating in the study. All patients received 100mg/kg of PZQ divided in four oral dosages of 25mg/kg each for one day only and 30 mg of prednisone daily during 4 consecutive days, and 150 mg of aspirin after breakfast. We obtained written informed consent from each patient.
Response to anti-parasite treatment were assessed by neurological evaluation of the CVD disease manifestation at the baseline and one week after the anti-parasitic treatment with PZQ, and also with CT Scan of the brain a week after. All patient received the same supporting treatment and were encouraged to eat rich carbohydrate meals and the same personnel evaluated all throughout the study.
An experienced neurologist evaluated all patients, none patients had no previous history of any other neurological disease apart from clinical manifestations of CVD. All patients presented with elevated systolic and diastolic blood pressure ranged from 146/93mmHG to 169/114 mmHg. (Table I)
Table I. Measurement of blood pressure
Although cognitive disorder and urinary incontinence were a common clinical signs in this group; however combination of memory dysfunction, difficulty walking, and stroke in all of them were also observed (Table II).
Table II. Commonest problems
Absolute criteria for NCC based on neuroimaging findings were present in all selected patients considering the cystic lesion with scolex (bright nodule within the cyst, producing the so-called "hole-with-dot" imaging) as patognomonic (Figure 1), LA was present in all patients, and lacunar infarct on the basal ganglia in six of them radiographically (Table III).
Table III. Radiography findings and sex
Figure 1 CT Brain Scan showing active NCC (left) and lacunar infarction on the head of the caudate nucleus (right) and leukoaraiosis
On physical examination one patient evidenced a mild improvement of gait after one single day therapy with praziquantel, one remained without remarkable changes and the other five worsened. (Table IV)
Table IV. Outcome after Praziquantel therapy
One patient developed generalized tonic-clonic epileptic attacks, other 2 died after coagulation disorders, deep venous thrombosis, massive pulmonary embolism, and ischemic hemorrhagic stroke (Figure 2) and microglial activation (Figure 3) the rest evidenced faster deterioration of the cognitive dysfunction and memory. Efficacy analysis included 7 patients (4 women and 3 man, mean age 65,17, years, range 60 to 71) treated with praziquantel/prednisone.
Patients with poorest prognosis evidenced signs of chronic arterial hypertension such as "onion-skin" changes in renal blood vessels (Figure 4)
From our personal experience BD is more common than the figure described by Gautier,7 and is characterized among other signs by subcortical neurological deficits such as gait abnormalities, rigidity, and neurogenic bladder plus psychiatry disorders including mood changes and depression, loss of memory and cognition, hypertension, evidence of systemic vascular disease or disease of the large blood vessels in the neck, stroke, blood abnormalities, and disease of the heart valves in people oldest than 60 years.
Two millions of biomedical articles are published every year, after review of some of them we found no evidence for treat all patients with NCC12 or insufficient evidence to assess whether cysticidal therapy in NCC is associated with beneficial effects (2002 Cochrane Database of Systematic Reviews)13 in other articles we found small population for the study, no radomization and double blindness, no control group, no adequate outcome measuring, wrong statitistical analysis, no inclusion or exclusion criteria, poor discussion of the results and some bioethical problems.14 15 16 17 18 19 In spite of the above-mentioned mistakes on research planning, we personally believe that some symptomatic patients without any other associated neurological disorder require anti-cysticidal therapy for NCC.
Although the role of alterations of the blood-brain-barrier linked to hypertensive episodes with chronic vasogenic edema in patients with BD is not well defined, the role of platelet activation as a major participant in the etiology of thromboembolic stroke is well known.