A 47-year-old man presented with a 9-year history of a hypoalert hypoactive behaviour syndrome, caused by the deep brain swelling variant of spontaneous intracranial hypotension. Along with apathy with retained cognition, he had stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a sagging brainstem, pointed ventricles and reduced angle between the vein of Galen and the straight sinus, but no meningeal enhancement or subdural collections. A dopamine transporter scan showed preganglionic dopamine receptor deficiency; a fluorodeoxy glucose positron emission tomography scan showed bilateral hypothalamic hypometabolism. This variant of spontaneous intracranial hypotension may alter deep brain functioning within the basal ganglia and thalamus, causing the hypoactive-hypoalert behaviour phenotype.
- Clinical neurology
- Behavioural disorder
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Intracranial hypotension may present with postural headache, tinnitus and changes in conscious level. Less commonly, spontaneous intracranial hypotension manifests as its ‘deep brain swelling variant’.1 We present a man with a 9-year history of this, and suggest that dopamine receptor deficiency and thalamic hypometabolism explains his hypoactive-hypoalert behaviour syndrome.
A 38-year-old man presented with a 2-year history of behaviour change. He had previously been energetic, quick-witted and fastidious about his appearance. He had shown subacute onset of neglect of personal appearance and hygiene, with reduced spontaneity and appearing to be asleep or motionless for prolonged daytime periods. He seemed unbothered about losing his job. There was no orthostatic headache. He developed dysarthria, drooled saliva and had impaired swallowing, requiring a soft diet. He smoked cigarettes, drank no alcohol and did not use illicit drugs. There was no relevant family history.
On examination, he showed paroxysmal stereotyped posturing, with slow truncal and neck flexion, partial head turning to the left and slowly rubbing his face with his left hand. He was hyper-reflexic and had bilateral extensor plantar responses. Upgaze was restricted and gait was mildly ataxic with reduced arm swing. If stimulated and continually prompted, he could complete relatively complex motor and cognitive tasks.
MR scan of brain showed midbrain and pontine enlargement and signal change within the pyramidal tracts, but no meningeal enhancement (figure 1A,B). The imaging appearances were consistent with the deep brain swelling variant of spontaneous intracranial hypotension. Sequential MR brain scans over the subsequent 9 years showed no change. Heavily-weighted T2-myelographic MR scan of spine found no source of cerebrospinal fluid (CSF) leak. A dopamine transporter scan (DaTscan) showed loss of dopamine reuptake transporters in both putamen (figure 1C). Fluorodeoxy glucose positron emission tomography (FDG PET-CT) showed reduced activity within the grey matter of the left occipital and temporal lobes and marked hypometabolism in both thalami, with near-absent activity on the left (figure 1D–F show further details). Polysomnography identified central apnoea episodes. Neuropsychological evaluation showed a severe deficit of self-initiation of thought, action and goal-directed behaviour, in keeping with hypoactive-hypoalert behavioural syndrome (table 1).
Three epidural blood patches each gave transient and subjective improvements in spontaneous conversation and activity reported by his family, but with no sustained objective improvement. A dopamine agonist (ropinirole up to 18 mg daily) had to be stopped as he developed impulse control disorder with hypersexuality. A subsequent trial of L-dopa (co-beneldopa up to 125 mg five times daily) had no benefit and similar side effects, and so was also stopped. Nine years after presentation, he still has severe apathy, requiring assistance with activities of daily living. MRI shows that the angle between the vein of Galen and the straight sinus has remained stable at 21°(figure 2).
Apathy—a quantifiable reduction in voluntary, goal-directed behaviour2—may arise from disruption of emotional-affective, cognitive and autoactivation processing. Apathy from an autoactivation deficit is termed hypoactive-hypoalert behaviour or ‘psychic akinesia’2 and is due to difficulty in self-activating thoughts or behaviour, with preserved ability to generate externally driven behaviour. Hypoactive-hypoalert behaviour is characterised by severe apathy and stereotyped activity that can be temporarily abated by external stimulation. It can arise from lesions in striatopallidal and caudate nuclei, thalamus and frontal white matter.3–5
This patient has a hypoactive-hypoalert behaviour phenotype and imaging findings consistent with the deep brain swelling variant of spontaneous intracranial hypotension. Whereas the more commonly recognised form of spontaneous intracranial hypotension often has typical radiological features including subdural fluid collections and enhancement of thickened dura, people with the deep brain swelling variant do not always have such features but rather may have severe brain sagging with swelling of the diencephalon/mesencephalon structures.1 Heavily T2-weighted MR myelography, which is at least as sensitive as CT myelography in detecting spinal CSF leaks,6 failed to identify a spinal leak. Previously reported cases of this syndrome have shown FDG PET-CT hypermetabolism in the pontine-mesencephalic region and hypometabolism of the prefrontal cortex bilaterally.7 However, our patient’s imaging showed markedly reduced bilateral thalamic activity. Glucose hypometabolism of the thalamus and hypothalamus occurs in narcolepsy.8 The thalamus has an integral role controlling arousal, affect, cognition and autoactivation.2 Anatomical change associated with the deep brain swelling variant of spontaneous intracranial hypotension may disrupt mesencephalic neural pathways, causing a reduction in excitatory or an increase in inhibitory projections to the thalami. Reduced thalamic excitation may diminish activity of the frontal cortex.
Vasogenic oedema probably causes swelling in the deep brain swelling variant of spontaneous intracranial hypotension, as increased diffusivity has been demonstrated in deep structures.1 People with this variant show a reduced angle between the vein of Galen and the straight sinus, probably through a functional stenosis causing venous stagnation, with subsequent venous hypertension, vasogenic oedema and deep brain swelling.1 The vein of Galen and the straight sinus angle in our patient was 21° compared with a mean of 73° in controls.1 We suspect that the observed thalamic hypometabolism was due to venous stagnation and vasogenic oedema disrupting mesencephalic neural pathways.
Some patients with this syndrome show reversals of stupor, coma, parkinsonism and dementia after treatment of spontaneous intracranial hypotension9 10 as well as transient responses to treatment.7 One patient’s recovery was associated with improved cortical perfusion on FDG PET-CT after epidural blood patch.11 Although there was a small increase in the angle between the vein of Galen and the straight sinus, there was only minimal resolution of deep brain swelling on MRI, suggesting that even a mild increase in the angle between the vein of Galen and the straight sinus may decrease venous stagnation and improve cerebral perfusion. Our patient’s poor treatment response suggests an ongoing CSF leak and persistent intracranial hypotension or chronic deep brain swelling due to spontaneous intracranial hypotension with irreversible structural brainstem changes. In follow-up over 9 years there has been no clinical or MRI progression or change.
Our patient’s FDG PET-CT and DaTscan neuroimaging abnormalities reinforce the clinical phenotype of the deep brain swelling variant of spontaneous intracranial hypotension, particularly as brain MRI findings alone correlate poorly with symptom severity. Dopamine transporter deficiency has not been previously reported in this syndrome. Although MRI appearances consistent with low pressure may occur asymptomatically12 our patient’s clinical findings, dopamine transporter deficiency and thalamic hypometabolism suggest an expanding spectrum of the deep brain swelling variant of spontaneous intracranial hypotension.
Spontaneous intracranial hypotension can present with different phenotypes including a deep brain swelling variant with a hypoactive-hypoalert behaviour syndrome (also known as psychic akinesia).
The angle between the vein of Galen and the straight sinus is reduced in patients with the deep brain swelling variant of spontaneous intracranial hypotension, compared with normal controls.
Bithalamic hypometabolism may explain the hypoactive-hypoalert behaviour syndrome in patients with the deep brain swelling variant of spontaneous intracranial hypotension.
Contributors SK wrote the first draft and contributed to the revisions.
PF drafted neuroimaging text and figures and revised drafts of the paper.
SH drafted neuroimaging text and figure and revised the paper.
WS provided neuropsychometry data and revised drafts of the paper.
MOM conceived the idea of publication, coordinated preparation, submission and revisions.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Masud Husain, Oxford, UK.
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