Subacute onset fluctuating sensorium, mimetic facial palsy and vertical supranuclearophthalmoplegia in an young female.

Case Report

A twenty eight year old female delivered a baby 5 months before presentation. She started experiencing repeated episodes of blackouts in front of her eyes, since two weeks. These consisted of brief spells of diminishing of vision and inability to comprehend the surroundings lasting for a few seconds and passed off completely. She did not have falls or accidents due to these episodes. Along with these episodes, she developed a dull headache, lasting few hours every day, bilateral, frontal and was not associated with nausea or vomiting. She was able to continue her daily activities in spite of the headaches. The problem increased further when her relative noticed her to have a generalized tonic clonic convulsion, frothing at mouth and loss of consciousness lasting for 8-10 minutes. She remained confused for the next few hours and returned to normal. Her behavior gradually changed and she spoke only few words, low in volume without associated emotions. She would remain silent most of the day. She became slow in her routine activities. She found it difficult in maintaining her balance in sitting position, and would sway backwards whist sitting and standing. Her relatives noticed that when she smiled, her mouth deviated to left side. Gradually she became sleepier in daytime. Over these days she became further slow and eventually became bedbound. She could not stand without support. It was noticed that she had difficulty in holding objects with her right hand. She passed urine in clothes. Curiously, her relatives noticed fluctuation in her alertness in 3-4 days before coming to the hospital. During these days sometimes she used to be normal intermittently responding to verbal interactions, speaking few words and again after some time she would become drowsy. Relatives retrospectively felt that her disease could have begun earlier with some slowing and lack of interest which was put down to the puerperal setting and tiredness. There was no history of dysphagia, nasal regurgitation, fever or neck pain. There was no history of sensory complaints in the limbs, nor any visual impairment. She had not had any joint pains/recurrent abortions/deep venous thrombosis. There was no history of seizures or recurrent headache in past.

Patient was afebrile with pulse 80/min regular and blood pressure of 124/80mmHg. There was no significant postural fall of blood pressure. There were no signs of meningeal irritation. She had no pallor, clubbing, cyanosis, lymphadenopathy, edema or pain in the lower limbs.

Wide fluctuations of level of consciousness were noted while she was in the wards. At times she would be conscious and responded appropriately to verbal interactions, with some impaired attention. At other time, often only few hours apart, she would become unresponsive, only opening her eyes to painful stimuli. These episodes of intermittent drowsiness continued for 2-3 days and then she became unresponsive. At that time her Glasgow Coma Scale was 10.

Examination in the early stages before the persistent unresponsiveness developed, showed her speech output to be reduced with hypophonic, monotonous melody. Higher mental status could not be analyzed satisfactorily at any time due to her impaired attention, even when she was at her best. Pupils were bilaterally normal, equally reacting to light. External ocular movements were restricted in vertical gaze, upward more than downward, with preserved vestibulo ocular reflex suggestive of supranuclearophthalmoplegia.

On motor system examination she had right sided pronator drift, brisk reflexes in both upper limbs (right more than left) and extensor Babinski sign. Power examination was not possible in detail but still showed right more than left sided pyramidal pattern of weakness. Sensory examination was difficult to comment upon.

Her complete blood count, liver function tests and kidney function tests were normal. Also her repeated electrolyte examinations during ward stay were normal. Her HIV, HBsAg and VDRL were non reactive. Her CSF examination was showing no cells with proteins of 26mg% and sugar 48mg% with normal opening pressure. MRI was done [Figure 1].

Figure 1

MRI of Brain showing bilateral diffusely swollen thalami, which are non enhancing and hyperintensities across midbrain as well as temporal lobes. All the changes were prominent on left side. (a) T1 Axial (b) T2 Axial (c) T1 post gadolinium (d) Flair axial. The post gadolinium T1 axial image shown in E, was after 7 days of the initial images suggestive of dense intraventricular enhancement

Discussion Related to Localisation

A 28 year old young female had delivered 5 months ago. She became symptomaticsince 2 weeks prior to admission; however, she was having some lack of interest and slowing in her post- delivery period and it was attributed to tiredness and post partum status. Since 2 weeks she started having intermittent spells of loss of vision and inability to comprehend surroundings lasting for few seconds; are they visualobscurations (VO) or seizures? In pure visual obscuration there would be no impairment of comprehension of surroundings. Occipital lobe seizures may present with ictal blindness; the spread of electrical discharge to temporal lobe may cause alteration in level of consciousness; this aura may or may not be followed by a generalised seizure.[1] On the other hand the episodes of VO are very short lived lasting for few seconds. Therefore these occurrences of loss of vision would be attributed to raised ICP with bilateral papilloedema. Since 2 weeks she was also complaining of headache that was bilateral and frontal, possibly mild to begin with as it did not interfere with her daily activities. In this period she had a generalized seizure. Seizure is a cortical event but it can also occur as the sub- corticalpathology encroaches upon the cortex or due to raised ICT like hydrocephalus or mass effect. Around the same time she had change in her behavior; her speech was hypo- phonic and sparse; she had lack of emotions and she became silent and slow. The lack of emotions, apathy, slowness, hypophonic speech are suggestive of frontal lobe affection; but similar behavioral patterns are seen in diseases of subcortical structures that projects to the frontal lobes. The Frontal- subcortical dementia is due mainly to subcortical pathology with slowness of thought process, inability to manipulate knowledge and associated behavioral changes like apathy inertia etc. She had gradual difficulty in maintaining balance. She was noted to have facial drooping while smiling; movements of the lower half of the face on volition were normal- these features were of Mimetic facial palsy [Table 1].[2] Gradually she became drowsy during daytime and became bedbound. She was passing urine in clothes and showed fluctuations in her level of consciousness. She possibly had righthand weakness. From history we gatheedr that a younglady, five months after her delivery, shows a progressively rapid downhill course. She shows features of visual obscuration suggestive of raised ICP; throws a GTC and shows behavioral features of Frontal- subcortical dementia. She shows a right mimetic supranuclear VIIth nervepalsy along with right upperlimb weakness. She gradually becomes bedbound, drowsy and incontinent in 2 weeks of time

Table 1

Mimetic facial palsy

From the above one would suspect the lesion to be deep cerebral possibly involving basal ganglia, capsular area/thalamus on the left causing hydrocephalus/mass effectd ementia and right sided weakness. On CNS examination she was drowsy, was having hypophonic monotonous speech with reduced speech outcome. She had fluctuations in level of consciousness which lasted for 2-3 days and then she became unresponsive. She had poor attention span. The pupils were equal and reactive to light. She had vertical gaze palsy, upward more than downward with preserved vestibulo -ocular reflexin horizontal direction. Fundus examination showed bilateral grade IVpapilloedema. She had right emotional palsy with preserved volitional control of the face.The motor system revealed right sided weakness with bilateral brisk reflexes in upper limbs, Rt+++, Lt++. She had bilateral pyramidal weakness right side being more affected than the left. The Babinski response was extensor on the right.

From the clinical examination, the lesion is bilateral, right side being more affected than the left.

Three important signs helpin localizing the lesion 1. Mimetic facial palsy, 2. Vertical gaze palsy and 3.The type of dementia.

Anatomically the lesion is localized to the upper brainstem/diencephalon. In view of dementia the lesion is more likely to be thalamic than upper brainstem.

The pathological process is rapidly progressive causing raised ICP/mass effect with visual obscurations due to papilloedema; the mass may be causing rapidly progressing high pressure hydrocephalus.

According to MRI Brain the lesion was localized to bilalateral thalami with involvement more on left side. The following discussion is for bilateral thalamic lesions

Differentials of bilateral thalamic lesions

Deep cerebral vein thrombosis.

Bilateral thalamic infarcts

Secondary to “top of the basilar” syndrome

Secondary to artery of Percheron infarcts

Viral encephalitis

Bilateral thalamic glioma

Cruetzfeldt Jacob disease

Deep cerebral vein thrombosis

Deep cerebral vein thrombosis (DCVT) is due to thrombosis of internal cerebral veins and/or vein of galen. These cases have higher mortality. These patients usually present with confusion, disorientation and progression to comatose stage within a short span. In a retrospective review of 49 patients with DCVT, the presenting features were confusion, coma, or mental status changes (76%); headache (63%); nausea and/or vomiting (41%); hemiparesis (33%); seizure (14%); fever (12%); papilledema (10%); and aphasia (6%).[3] These cases have strong female preponderance (8:1 ratio3). The risk factors in majority of cases include polycythemia, oral contraceptives, malignancy, pregnancy, and puerperium, and inflammatory bowel disease. To sum up, then DCVT is characterized by a high female predominance, the presence of a rapidly declining clinical course with headaches, nausea, vomiting, altered consciousness, and long tract signs, and absence of the papilledema, seizures, and focal deficits characteristic of dural sinus thrombosis. On MRI these cases have bilateral thalamic hyperintensities with sometimes having basal ganglia, periventricular white matter and portions of cerebral peduncles. MR venography reveals thrombosis of deep venous system as absence of flow void. DCVT was ruled out in our patient by normal MR venography, involvement of midbrain, temporal lobes and contrast enhancement within very short duration (3 days). But clinically patient simulates DCVT.

Bilateral thalamic infarcts

Thalamus is supplied by four main arteries as shown in Figure 2.

Figure 2

Arteries supplying thalamus[3]

These are the tuberothalamicartery,the paramedian artery, the inferolateral arterial group, and the lateral posterior choroidal arterial group.

The artery of percheron (AOP), is a single paramedian trunk, arises from one or the other P1 portion, and then supplies both medial thalami. Thus, if this artery becomes compromised, the result is bilateral paramedian thalamic infarcts.

In the series of Bogousslavsky et al, out of 14 patients with paramedian thalamic infarcts, 5 were bilateral.[5] In another series by Osborn et al, of 37 patients, 4 ischemic patterns of AOP infarction: 1) bilateral paramedian thalamic with midbrain (43%), 2) bilateral paramedian thalamic without midbrain (38%), 3) bilateral paramedian thalamic with anterior thalamus and midbrain (14%), and 4) bilateral paramedian thalamic with anterior thalamus without midbrain (5%). A previously unreported finding (the “V” sign) on FLAIR and DWI sequences was identified in 67% of cases of AOP infarction with midbrain involvement and supports the diagnosis when present.[6] Similar infarcts may be seen with top of basilar artery syndrome where there is thrombus in distal basilar artery. In that condition, the paramedian thalamic infarcts tend to be part of a more extensive infarct which includes midbrain and the PCA territories. Clinically these patients had disorder's consisting of consciousness, memory dysfunctions, various types of vertical gaze paresis, and psychological changes. Sometimes these cases have hypersomnolence as a manifestation of Kleine Levine syndrome.

In our patient symptoms evolved over a period of time. Also radiologically MR angio was normal, there was no diffusion restriction and involvement was more than paramedian region (more of whole thalamus is involved). So bilateral thalamic infarcts was considered less likely in present situation.

Viral encephalitis or autoimmune encephalitis

Viral encephalitis was strongly considered in our case initially before the contrast enhancing MRI was seen. Likely etiologies considered Japanese encephalitis, West nile virus encephalitis and Murray valley encephalitis. Japanese encephalitis according to Mishra et al, has bilateral thalamic involvement in most cases along with involvement of basal ganglia, midbrain and temporal lobes.[7] But most of the thalamic lesions were non haemorrhagic and non enhancing. Also presentation of Japanese encephalitis frequently includes dystonia and other movement disorders. In West nile virus encephalitis MRI is usually normal in most patients. However, abnormalities have also been described such as lesions in the focal cerebral hemispheric white matter, pons, substantial nigra, and thalamus with increased signal intensity on T2-weighted images.[89]

Clinically meningitis and encephalitis is usually associated with acute flaccid paralysis. A case report of Murray Valley encephalitis, a disease seen almost exclusively in Australia, showed marked bilateral thalamic involvement. The imaging pattern was very similar to the reports of Japanese encephalitis, but with disease even more focused on the thalami in this particular case. But midbrain and temporal lobe involvement along with contrast enhancement was unusual for Murray valley encephalitis. Also being uncommon in India it was considered low in differential diagnosis. Last in differential diagnosis was HIV encephalitis which can have bilateral thalamic involvement.

In this patient, CSF was normal, so encephalitis as a possibility was less likely. The intraventricular contrast enhancement within a short time was uncommon with any viral encephalitis.

Another differential considered was autoimmune encephalitis as limbic encephalitis. But in limbic encephalitis there is more involvement of bilateral medial temporal lobes rather than bilateral thalami, which is seen predominantly in our case. Also the clinical findings as vertical supranuclearophthalmoplegia and short duration of illness less likely. In limbic encephalitis clinically patient has memory dysfunction with fluctuating illness, sensorium is affected in later stages, which was very early in our case.

Bilateral thalamic gliomas

Bilateral thalamic gliomas are rarely reported in literature and most of the reports suggest low grade astrocytomas (WHO Grade II). In one of the survey at Montreal neurological institute and hospital from 1963 to 1991, only 8 cases have been found.[10] In another series of four cases, Grade II astrocytomas were seen with survival up to months to years.[11] Other individual case reports are available. Most of the cases presented with history within months to years as they grow slowly. The diagnosis is based upon biopsy and there are very limited therapeutic options in such cases.

In our case patient was having non enhancing bilateral swollen thalami. Surprisingly there was involvement of midbrain and temporal lobes. Initially there was a dilemma for diagnosis, but when MRI was repeated after 3 days which showed dense intraventricular enhancement and MR spectroscopy was showing large choline peak, possibility of high grade gliomas was considered more likely and biopsy was decided.

Final diagnosis

Through transcallosal approach, biopsy was taken through bilateral thalami on day 15 of admission. The histopathology revealed moderately diffuse infiltrating high grade glial tumor. The tumor showed pleomorphic astrocytic cells with marked nuclear atypia and brisk mitotic figures which suggested anaplastic astrocytoma (WHO Grade III) [Figure 2]. On immunohistochemistry, tumor was negative for P53 and Mib labeling index was 15-20%. [Figure 3]

Figure 3

Histopathology showing moderately diffuse infiltrating pleomorphic astrocytic cells with marked nuclear atypia and brisk mitotic figures

Her condition deteriorated and developed hydrocephalus for which bilateral ventriculoperitoneal shunt was put. Till last follow up she was in a moribund state on supportive treatment.