Blepharospasm BSP is a rather distressing form of focal dystonia. Although many aspects of its pathophysiological mechanisms are already known, we lack fundamental evidence on etiology, prevention, and treatment. To advance in our knowledge, we need to review what is already known in various aspects of the disorder and use these bases to find future lines of interest. Some of the signs observed in BSP are cause, while others are consequence of the disorder. Non-motor symptoms and signs may be a cue for understanding better the disease. Various cerebral sites have been shown to be functionally abnormal in BSP, including the basal ganglia, the cortex, and the cerebellum.
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Blepharospasm BSP is a rather distressing form of focal dystonia. Although many aspects of its pathophysiological mechanisms are already known, we lack fundamental evidence on etiology, prevention, and treatment.
To advance in our knowledge, we need to review what is already known in various aspects of the disorder and use these bases to find future lines of interest. Some of the signs observed in BSP are cause, while others are consequence of the disorder. Non-motor symptoms and signs may be a cue for understanding better the disease. Various cerebral sites have been shown to be functionally abnormal in BSP, including the basal ganglia, the cortex, and the cerebellum.
However, we still do not know if the dysfunction or structural change affecting these brain regions is cause or consequence of BSP. Further advances in neurophysiology and neuroimaging may eventually clarify the pathophysiological mechanisms implicated. In this manuscript, we aim to update what is known regarding epidemiology, clinical aspects, and pathophysiology of the disorder and speculate on the directions of research worth pursuing in the near future.
Blepharospasm BSP is a form of focal dystonia that manifests with spasms of the eyelids, involuntary closure of the eye, and enhanced spontaneous blinking, or any combination of the previous ones. We have advanced in our knowledge of the disorders since the first descriptions of BSP as a form of dystonia 1 , 2. However, there are still many unknown aspects in the generation of the disorder and unclear points in the pathophysiological mechanisms of the various forms of focal dystonia.
BSP is particularly distressing. Patients may be functionally blind and unable to pursue a normal social life, with plenty of emotional and behavioral consequences. Although BSP is now recognized as one of the most common forms of adult-onset dystonia, it is thought to be rare, affecting about 16— cases per million 3.
BSP patients may also have tremor in the head or upper limbs 5. Blepharospasm is characterized by stereotyped, bilateral, and synchronous spasms of the orbicularis oculi muscles.
Spasms may be brief or sustained and may induce narrowing or closure of the eyelids. Other relevant manifestations include: sensory trick that can transiently improve eyelid spasms in about half of the patients 6 , associated apraxia of eyelid opening 7 , and increased spontaneous blink rate 8. Whether increased blinking may preceed BSP is an open question for future studies 9.
The new severity scale was based on six clinical aspects, including degree and duration of eyelid closure, frequency of spasms, presence of apraxia of eyelid opening, occurrence of spasms during writing and increased blinking. The scale is suitable to assess BSP severity in clinical practice and research, yielding moderate to almost perfect reliability and acceptable clinimetric properties 5 , Several non-motor manifestations may be more frequent in BSP patients than in healthy or disease controls.
They belong to four domains: sensory symptoms, psychiatric disorders, sleep disorders, and cognitive disturbances. Symptoms belonging to the sensory domain include burning sensation and grittiness in the eye, dry eye, and photophobia. Psychiatric alterations include depression, anxiety, and obsessive—compulsive disorders 13 , The finding is not specific because psychiatric disturbances, mostly depression, are also more frequent in patients with various forms of focal dystonia than in healthy controls.
Theoretically, psychiatric disorders may be part of the clinical spectrum of the disease or secondary to the dystonia-induced disability. By most studies, depression appears to represent a feature of primary dystonia, whereas other psychiatric abnormalities have a less certain relationship and need additional evaluation. Sleep impairment may be another feature of BSP It seems to be independent of motor severity but rather correlated with depression. Therefore, it is not clear at present if there is a primary sleep abnormality in dystonia.
Further studies are warranted. There is little evidence of alteration of cognitive functions in idiopathic dystonia. Nevertheless, a recent study showed that non-depressed and non-demented patients with cranio-CD and normal IQ may have impairments in several specific cognitive domains including working memory, information processing speed, and set-shifting capacity Altered cognitive measures were independent of the clinical expression of dystonia. As in other forms of focal dystonia, BSP is considered to originate from a dysfunction in basal ganglia circuitry, although other brain and brainstem circuits can also be involved.
Lesions causing BSP have been identified in various sites. In the analysis of their own cases, Khooshnoodi et al. In a total of 48 cases 30 of them extracted from the literature , these authors reported lesions in several parts of the brain, including the thalamus in 12, lower brainstem in 11, basal ganglia in 9, cerebellum in 9, midbrain in 7, and cortex in 1.
These observations have contributed to the idea of a widely distributed network of regions where lesions can potentially lead to BSP. Although evidence for lesions in patients with BSP is scarce, researchers on brain neuroimaging have found group abnormalities in various sites also. The first to report on volumetric abnormalities in idiopathic focal dystonia was Black et al. The authors speculated on the possibility that putaminal GMV change could be a response to dystonia if not related to its cause.
These authors observed also decreased GMV in the left inferior parietal lobe, which correlated significantly with duration of botulinum toxin treatment and suggested a crucial role for the putamen in the pathophysiology of focal dystonia and secondary changes related with the tonic spasms and their botulinum toxin treatment for the left parietal region.
However, not all studies confirmed the increase in volume and hyperactivity in the striatal region. Obermann et al. In this study, though the authors examined patients with BSP 11 together with patients with CD 9 in an attempt to find common sites of involvement shared by these two forms of focal dystonia.
In any case, they concluded that the morphometric changes found were located within structures important for sensorimotor integration and motor control, pointing out to a functional damage that, with time, may lead to structural changes.
Other authors reported no significant change in microstructure of basal ganglia using diffusion tensor imaging 7 or voxel-based morphometry The latter study is relevant for reporting, apart from the absence of changes in the basal ganglia, greater GMV in BSP patients than in healthy volunteers in the right middle frontal gyrus and the reverse pattern i.
Therefore, these authors concluded that patients may have cortical but no basal ganglia changes. It is difficult to know the cause of the differences in the findings reported by Martino et al.
Martino et al. However, it is difficult to believe that nine patients can account for the differences reported.
Other factors have to be taken into account to explain the different findings reported so far, such as age at disease onset, disease duration, presence of dystonia spread to other body sites, dystonia severity, and duration and mean dose of botulinum toxin treatment.
In none of these variables, the authors found a correlation with the neuroimaging findings but there can still be some influence from these variables enough to tilt the subtle abnormalities of BSP patients toward one or another direction. Involvement of the cortex and the corticonuclear tract was supported by another morphometric study 22 that showed a significant decrease in GMV in the facial portion of the left primary motor cortex and right anterior cingulate of BSP patients when compared to healthy volunteers.
An interesting comparison was made by Ramdhani et al. The authors concluded that these two forms of dystonia may have different pathophysiological mechanisms, may be precipitated by different triggers and express in neuroimaging as distinct microstructural patterns. The findings of Ramdhani et al.
They also put on show the contribution of the cerebellum as a key structure in the brain dystonia network 22 , Indeed, the latest findings in neuroimaging studies have revealed microstructural abnormalities in the cerebellum. Yang et al. BSP patients showed significant FA reductions in the left anterior lobe of cerebellum that correlated negatively with disease severity, while patients with BSP and oromandibular dystonia showed an increase of FA in the right parietal lobe that correlated negatively with disease duration.
Other abnormalities were also found in areas around the right precuneus, lentiform nucleus, and insula in different combinations in the two groups of patients. The authors concluded that white-matter changes outside the basal ganglia may present trait features that are specific for individual phenotypes of dystonia. Many functional abnormalities have been reported in BSP patients. In , Smith et al. A similar study on 10 patients with BSP showed increased glucose metabolism in the striatum and thalamus Two interesting additional observations were made in that study: five patients were investigated before and after treatment of muscle spasms with botulinum toxin and showed similar results, indicating that the abnormalities were intrinsic of the disorder and not the consequence of increased muscle activity.
On the other side, the authors did not find any significant correlation between severity of the spasms and the degree of striatum or thalamus hypermetabolism. Abnormalities in basal ganglia and frontal cortex have been reported since then, using various functional neuroimaging techniques, in various studies of patients with BSP Kerrison et al. They also found increased glucose uptake in the right caudate and decreased glucose uptake in the left inferior cerebellar hemisphere and thalamus.
Hutchinson et al. They found that during sleep, patients showed frontal hypometabolism in a region associated with cortical control of eyelid movements while they showed hypermetabolism of the cerebellum and pons during wakefulness, when they exhibited involuntary muscle contractions. Apart from that, network analysis demonstrated overactivity of the lentiform nuclei, cerebellum, and the supplementary motor regions, reported by the same authors previously to be a pattern of abnormalities associated with other forms of dystonia.
In a similar line of reasoning, Suzuki et al. They found significant increase in glucose metabolism in the thalamus and pons that they interpreted as an expression of a compensatory change, common to pathophysiological mechanisms in other types of focal dystonia.
The same authors have recently reported that the increase in putaminal glucose metabolism shown using FDG PET in patients with essential BSP may separate them from those with drug-induced BSP who did not show such increase.
A correlation between severity of the spasm and the intensity of increased glucose metabolism in the thalamus was reported by Murai et al. An interesting approach was taken by Emoto et al. These authors found that patients with photophobia had significant hypermetabolism in the thalamus, while those without photophobia had significant hypometabolism in the superior colliculus.
These findings may underlie mechanisms for the increase in the blinking rate in BSP patients with photophobia. A functional magnetic resonance imaging fMRI study with analysis of the blood oxygenation level-dependent signal was done during spasms by Schmidt et al.
Healthy volunteers were asked to make a voluntary closing of their eyelids that was to be contrasted with rest, while patients were requested to press a button to mark the onset of their spasms. The authors reported on various areas activated with blinking, common to patients and healthy subjects, such as frontal and parietal operculum, supplementary motor area, primary sensorimotor cortex, various visual areas, and the cerebellum.
The site where differences were observed was a subregion of the putamen, where the authors found hyperactivation in patients in comparison to healthy volunteers. Baker et al. The authors found greater activation in BSP patients than in control subjects in the anterior visual cortex, anterior cingulate cortex, primary motor cortex, central region of the thalamus, and superior cerebellum.
Therefore, their findings suggested the existence of a hyperactive cortical circuit linking visual cortex, limbic system, supplementary motor cortex, cerebellum, and supranuclear motor pathways innervating the periorbital muscles. The existence of an abnormal default mode network implying the cortico-striato-pallido-thalamic loop has been suggested by Zhou et al.
Dopamine binding has been also examined in BSP. The first report was made in by Perlmutter et al. This was confirmed by Horie et al. The authors speculated on the possible mechanism relating dopamine ligand striatal deficit and decreased inhibition in BSP, typical of all forms of dystonia. Dystonia is a functional disorder, and therefore, neurophysiology is a key methodology for its study, both for recognizing the underlying pathophysiological mechanisms and providing cues for the differential diagnosis when clinical signs and symptoms are not sufficiently clear.
In the case of BSP, the most useful neurophysiological test is the blink reflex, which can be used to examine the excitability of brainstem interneurons, modulated in turn by circuits feeding on basal ganglia output signals 39 —
Blepharospasm is abnormal contraction of the eyelid muscles. It often refers to benign essential blepharospasm BEB which is a bilateral condition and a form of focal dystonia leading to episodic closure of the eyelids. The exact cause of BEB is unknown and, by definition, it is not associated with another disease entity or syndrome. Symptoms usually begin as mild and infrequent spasms that progress over time to forceful and frequent contractures of the eyelids, in advanced cases causing functional blindness from inability to temporarily open the eyes. The first line treatment for BEB is periodic injection of botulinum toxin into the eyelid protractor muscles including the orbicularis oculi, corrugator supercilii, and procerus muscles.
Blepharospasm: Update on Epidemiology, Clinical Aspects, and Pathophysiology
Diagnosis Index entries containing back-references to G Toggle navigation. Type 1 Excludes. A type 1 excludes note is a pure excludes. It means "not coded here". A type 1 excludes note indicates that the code excluded should never be used at the same time as G
Isolated blepharospasm is rare and represents a minority of patients presenting with blepharospasm. Blepharospasm is commonly associated with lower facial spasms as part of a syndrome or disease complex. Some examples are: - Meige Syndrome: Characterized by spasm of the eyelids and midface. Generalized Dystonia: Presents with spasms across various body parts in addition to blepharospasm and facial spasms.
Blepharospasm is any abnormal contraction or twitch of the eyelid. The condition should be distinguished from the more common, and milder, involuntary quivering of an eyelid, known as myokymia. In most cases, blepharospasm symptoms last for a few days and then disappear without treatment, but in some cases the twitching is chronic and persistent, causing life-long challenges. In these cases, the symptoms are often severe enough to result in functional blindness. The person's eyelids feel like they are clamping shut and will not open without great effort.