Russian Journal of Woman and Child Health
ISSN 2618-8430 (Print), 2686-7184 (Online)

Worster-Drought syndrome. Neurological pattern (case report)

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DOI: 10.32364/2618-8430-2022-5-1-90-96

L.M. Shchugareva1,2, O.V. Poteshkina1,2, V.D. Petrova2, P.A. Salamanov2

1Children’s City Hospital No. 1, St. Petersburg, Russian Federation

2I.I. Mechnikov North-Western State Medical University St. Petersburg, Russian Federation

Worster-Drought syndrome (WDS) is a rare neurological disorder characterized by dissociation of voluntary and involuntary movements of the face, mouth, tongue, dysarthria, and oromotor dyspraxia. WDS rate varies from 1–9 per 100,000 to 1 per 25,000–30,000 newborns. Anterior (frontal) operculum, including the lower Rolandic area. WDS is diagnosed in the neonatal period based on a typical phenotype and neuroimaging findings. The prognosis is determined by medical care, epilepsy management, and rehabilitation. We describe a child with a severe WDS phenotype. In this child, abnormal intrauterine neuronal migration was associated with established cytomegalovirus meningoencephalitis in the neonatal period. Moreover, phenotypic signs (dissociation of voluntary and involuntary movements, dysarthria, severe salivation, microcephaly, and epilepsy) were coupled with neuroimaging findings (bilateral polymicrogyria of the opercular area and microcephalia). Pediatricians should be awa re of WDS clinical polymorphism. The knowledge base is upgraded annually.

Keywords: Worster-Drought syndrome, congenital pseudobulbar palsy, seizures, dysarthria, developmental delay, microcephalia, polymicrogyria.

For citation: Shchugareva L.M., Poteshkina O.V., Petrova V.D., Salamanov P.A. Worster-Drought syndrome. Neurological pattern (case report). Russian Journal of Woman and Child Health. 2022;5(1):90–96 (in Russ.). DOI: 10.32364/2618-8430-2022-5-1-90-96.

Background

Worster-Drought syndrome (WDS), or congenital pseudobulbar palsy, is a rare neurological disease. According to published data, WDS rate varies from 1 to 9 per 100,000 to 1 per 25,000–30,000 newborns [1].

This syndrome was initially described by Charles Worster-Drought, an English neurologist and founder of the Moor House School (Oxted, UK) specializing in speech and language disorders [2, 3]. Originally, WDS was described as a congenital suprabulbar tongue and pharyngeal paresis without specifying the level of impairment [3]. Meanwhile, the insula (an area located deep in the Sylvian sulcus and covered by the frontal, parietal, and temporal lobes together forming the operculum) is now considered to be affected (see Fig. 1) [4].

Рис. 1. Анатомия островковой доли [4] Fig. 1. Insula anatomy [4]

The anterior (frontal) operculum, including the lower Rolandic area, is affected in WDS [2]. Worster-Drought suggested that corticobulbar pathways passing from the lower motor cortex to the nuclei of cranial nerves X and XII are affected [5]. Pathways to the nuclei of cranial nerves V, VII, IX, X, and XII are currently known to be involved [2].

According to the published data, WDS is a congenital variant of the Foix–Chavany–Marie syndrome (FCMS), also known as bilateral opercular syndrome. Some authors suggest that these syndromes should be referred to as perisylvian dysfunctions [2, 6, 7]. FCMS is an acquired, usually bilateral, disorder of the frontoparietal operculum. This polyetiological syndrome is secondary to vascular events or meningoencephalitis (typically caused by herpex simplex virus and cytomegalovirus) or a part of epileptic encephalopathies [2].

WDS etiology is disputable. However, most authors believe in the theory of intrauterine impairment of neuronal migration, primarily in the perisylvian area [2, 8]. In contrast to FCMS, family history of congenital pseudobulbar syndrome was described. The genetic nature of this disorder is suggested [2, 9]. Finally, there are indications of infections, hypoxia, and other exposures on 20–24 weeks of pregnancy [2].

Genetic disorder in WDS is still unknown; several types of inheritance are suggested, e.g., X-linked dominant, X-linked recessive, autosomal dominant with reduced penetrance, and autosomal dominant [6, 7]. The role of mutations in the SLC9A1 (1p36.11 locus), SRPX2 (Xq22), and MECP2 (Xq28) genes, 22q11 deletions, and nonsense mutations in the LINS gene (p.Glu366X, p.Lys393X) is discussed [6, 7].

Clinical manifestations, treatment, and prognosis of WDS

WDS affects the tongue, mouth, lip, and soft palate muscles and, in severe cases, laryngeal and pharyngeal muscles [10, 11]. Disease onset occurs in the first year of life. However, WDS diagnosis is established mainly at the age of 5–6 or later [9]. The disease usually starts with abnormal sucking, but airway obstruction has also been reported. Meanwhile, nutrition disorders become more evident after shifting from breastfeeding to denser supplementary feeding [8].

Children with WDS have a typical appearance, i.e., hypomimia, mouth half open, hypersalivation [2]. Characteristic dysarthria or anarthria results from impaired voluntary control of facial, lingual, pharyngeal, and mastication muscles. Meanwhile, autonomous emotional innervation is preserved. This phenomenon is accounted for by the fact that involuntary movements are processed by the basal ganglia but not corticobulbar associations [2]. Additionally, WDS is an opercular variant of suprabulbar palsy. As a result, in contrast to the pontine variant of pseudobulbar palsy, pathological laughter and crying are missing in WDS [2]. In contrast to the bulbar syndrome, muscle atrophy with fasciculations and the lack of the jaw jerk, gag, and palatal reflexes are not typical for the pseudobulbar syndrome [2, 5, 10].

Chewing impairment (resulting from inability to move the tongue required for creating a bolus and advancing it to the pharynx) is an important characteristic of WDS. Meanwhile, gag reflex is unaffected [2]. Pseudo-peripheral facial palsy without Bell’s palsy (only m. orbicularis oris is affected, as a result, mimics is preserved) is also typical of WDS [2, 12]. Finally, WDS is characterized by rhinolalia associated with difficulties in reproducing lingual and labial consonants [13].

Incomplete WDS is characterized by speech impairment, i.e., oromotor dyspraxia, usually associated with hypersalivation. Therefore, only muscles of the tongue, lips, and soft palate are affected in mild WDS [8].

Specific tests to detect voluntary and involuntary dissociation are available. A child cannot put the lips in a tubule, the tongue is immobile. These children are asked to put out their tongue and move it back and forth and in different directions. However, even in mild variants, only putting out the tongue is possible [2]. Additionally, other tests are available, e.g., whistling, yawning, teeth chattering, slurping, chuckling, cheering, blowing, sniffing, touching the nasal tip with the tongue, etc. [14]. Notably, these movements are possible in distraction or mental strain, when a child inadvertently performs most of the proposed actions [2, 14].

In addition to pathognomonic symptoms, WDS patients have other neurological disorders. The involvement of cranial nerves V, VII, IX, X, and XII is reported in 80%-99%, dysarthria in 80%-99%, epileptic seizures in 29%-87%, cognitive disorders, hyperreflexia, and salivation in 30%-79%, microcephaly, sensorineural hearing loss, and pyramidal disorders in 5%-29%. The occurrences of ataxia, autism spectrum disorders, arthrogryposis, and micrognathia are unknown.

Epilepsy is one of the most common presentations of WDS (up to 87%) [2] and usually manifests with atonic and tonic hemifacial seizures (drop attacks) [15]. EEG typically shows generalized spike-and-wave complexes. Meanwhile, multifocal epileptiform discharges in the central parietal or central visceral regions are observed in 30% [2].

The diagnosis of congenital pseudobulbar palsy is established by clinical presentations and brain MRI. Typical neuroimaging findings are abnormally verticalized, enlarged, and in-depth sylvian fissures, bulging of the islands of Reil, enlargement and an abnormal location of the central sulcus, cortical dysplasia with abnormal thickening of the insular-opercular cortex on T2-weighed images, and polymicrogyria on T1-weighed images [2, 4]. These patterns are often bilateral [2].

Polymicrogyria (or non-lissencephalic cortical dysplasia) is a pathological change of the brain cortex presented with multiple short, shallow gyri [2]. WDS is characterized by four-layer polymicrogyria occurring in the abnormal development of the brain cortex at 20–24 weeks of gestation [2]. The localization of the defect in the operculum is possibly accounted for by the pattern of vascular supply of this region provided by the terminal branches of the middle cerebral artery developing after 10 weeks of gestation [2, 4].

Worster-Drought investigated this disorder extensively. He stated that in most children (particularly, with incomplete WDS), speech improves as they grow older [3]. The gradual partial recovery of speech by adolescence was also established in further studies on congenital pseudobulbar palsy [2, 13]. Meanwhile, in children with a severe phenotype, the prognosis is unfavorable due to a high rate of cognitive disorders and associated epilepsy [15].

No specific treatment is available. A multidisciplinary approach is important for WDS management; psychological, behavioral, and speech therapy approaches are used. These children should be trained from birth to alternative ways of expressing themselves, e.g., gestures, symbols, or other communication tools [13]. Medical treatment for epilepsy is also important. Antiepileptic drug therapy is effective for most patients. However, pharmacotherapy resistance has been reported [2].

Case report

A 4-year-old girl was admitted to our hospital with repeated seizures. The child was born in a second pregnancy complicated by chronic pyelonephritis, cervical ectropion, threatened abortion (at 9 weeks of gestation), and Rh-negativity without antibodies. At 36 weeks of pregnancy, intrauterine growth restriction was diagnosed. The girl was delivered at 40–41 weeks of pregnancy (birth weight 2,400 g, birth body length 48 cm, head circumference 32 cm, chest circumference 31 cm, Apgar score 8/9). After delivery, purulent choriodeciduitis and chronic placental insufficiency were observed. On day 2, the newborn was admitted to the neonatal department; cytomegalovirus intraamniotic infection was established.

According to the outpatient chart, severe psychomotor development retardation was diagnosed. Difficulties with feeding since birth were noticeable, i.e., the girl could not suck and was fed by infusing formula from the bottle to the mouth but swallowed without choking. As a result, the child did not require nasogastric feeding. Since birth, hypersalivation has been reported. Difficulties with feeding became more obvious after introducing the dense complementary food. The child receives soft food. At the age of 3.5 years, tonic-clonic seizures appeared. Antiepileptic therapy with valproic acid (30 mg/kg/day) was started. Later, the child was switched to topiramate (5.6 mg/kg/day) because of hepatotoxicity of valproate.

Family history: lung cancer on the father’s side, neurofibromatosis on the mother’s side (in grandmother). RET mutation in the 16th exon (that is clinically irrelevant for this disorder; a proto-oncogene for medullary thyroid cancer) was identified.

At admission, the child’s condition was serious (Gross Motor Function Classification System/GMFCS level 5). Physically, microcephaly and protein-energy malnutrition grade 2–3 (head circumference 42.5 cm [less than 3%], chest circumference [less than 3%], body weight 9,000 g [less than 3%], and body length 95 cm [10%]) were detected (see Fig. 2).

Рис. 2. Пациентка А.Н., 4 года. Синдром Ворстер-Дроута Fig. 2. A 4-year-old girl with Worster-Drought syndrome

The girl merrily responds to the examination. Visual motor integration and praxis are underdeveloped. The child fixes her sight, briefly follows objects. Intermittent convergent strabismus  was revealed. Productive contact was on the emotional level. Auditory orienting responses were detected. Only sounds were present in the speech. The girl could transiently hold her head up. Body alignment responses were not established.

A specific phenotype of the child (i.e., hypomimia, mouth half open, and almost permanent salivation) was also significant. The child received soft food, no choking. Jaw-jerk, palatine, and gag reflexes were reduced. Tongue movements were virtually absent; however, opercular automatism (tongue smacking) was reported during feeding. Oral automatism reflexes were missing.

Muscle tone in the upper limbs was reduced, while muscle tone in the lower limbs was increased (pyramid-like, D=S). The tendon reflexes were lively, reflexogenic zones were enlarged (D>=S). A positive Rossolimo-Venderovich reflex and flexion contractures of the ankle joints were reported. No meningeal signs. Brain MRI was performed twice, i.e., at the age of 1 month and during this hospitalization (see Figs. 3 and 4).

Рис. 3. МР-изображения головного мозга девочки А.Н. в возрасте 1 мес. (слева) и в 4 года (справа). Синдром Ворстер-Дроута Fig. 3. Brain MRI of a girl with WDS at the age of 1 month (left) and 4 years (right). Worster-Drought syndrome

Рис. 4. МР-изображения головного мозга девочки А.Н. в возрасте 1 мес. (А) и в 4 года (B). МР-трактография (C, D, E, F). Синдром Ворстер-Дроута Fig. 4. Brain MRI of a girl with WDS at 1 month (A) and 4 years (B). MR tractography (C, D, E, F). Worster-Droug

Electroencephalography (EEG) which was performed several times (see Figs. 5 and 6) showed spike-and-wave activity in the temporal region.

Рис. 5. Электроэнцефалограмма дневного сна пациентки А.Н., 4 года Fig. 5. Daytime sleep EEG of a 4-year-old girl with Worster-Drought syndrome

Рис. 6. Электроэнцефалограмма с видеомониторингом пациентки А.Н., 4 года Fig. 6. Video-EEG monitoring of a 4-year-old girl with Worster-Drought syndrome

Excessive symmetrical high-amplitude spikes of β-activity (exalted sleep spindles?) in the central frontal regions were reported. The epileptiform activity in the frontal (bifrontal) regions, represented as spike-and-wave discharges with low indices, was detected.

Electroencephalogram represented in Fig. 6 was registered in standard conditions during non-rapid eye movement sleep (NREM), quiet and active (feeding, emotional reaction) wakefulness with eyes closed/opened.

A periodic regional slowing of background activity in the occipital region was identified. Neither epileptiform nor other pathological activities or ictal discharges were registered. Phenobarbital (4 mg/kg/day) which was added to antiepileptic therapy improved the child’s condition (reduction of epileptic seizures, improvement of general health and emotional reactions). The prognosis is determined by medical care, epilepsy management, and rehabilitation.

Discussion

Clinical presentations of WDS are diverse and include both complete and incomplete variants. Table 1 summarizes the comparative rates of clinical presentations according to the published data [3, 8].

Таблица 1. Сравнительная характеристика данных анамнеза и клинической симптоматики СВД [3, 8, 16] Table 1. Comparative characteristics of anamnesis and clinical presentations from published data [3, 8, 16]

Given the dissociation between voluntary and involuntary movements of the tongue and mimic musculature, predominance of dysarthria over dysphagia, oromotor dyspraxia, and the above-mentioned specific tests, congenital pseudobulbar syndrome can be suggested. Meanwhile, differential diagnoses are numerous and include Moebius syndrome (congenital uni- or bilateral palsy of facial and extraocular muscles, mental retardation, autism spectrum disorders), Goldenhar syndrome (microtia, facial muscle weakness, underdevelopment of the cheek, chin, and temporal bone, microphthalmia, microstomia), Fazio-Londe syndrome (facial muscle palsy, dysarthria, dysphagia, stridor, pyramidal signs, extraocular muscle palsy, ptosis), and Cayler syndrome (hypoplasia of muscles depressing the corner of the mouth, congenital heart defects, microcell, micrognathia, mental retardation).

Fascio-labio-pharyngo-lingvo-masseter palsy with voluntary dissociation is an important trait that helps differentiate between the opercular syndrome and pseudobulbar palsy resulting from bilateral suprabulbar damage [17]. The differences in the opercular syndrome are listed in Table 2.

Таблица 2. Дифференциальный диагноз бульбарного, псевдобульбарного и оперкулярного синдрома у пациентов с дисфагией и дизартрией [17] Table 2. Differential diagnosis of the bulbar, pseudobulbar and opercular syndromes in patients with dysphagia and dysart

Conclusions 

We describe a child with a complete WDS of the severe phenotype. In this child, abnormal intrauterine neuronal migration was associated with established cytomegalovirus meningoencephalitis in the neonatal period. Moreover, phenotypic signs (dissociation of voluntary and involuntary movements, dysarthria, severe salivation, microcephaly, and epilepsy) were coupled with neuroimaging findings (bilateral polymicrogyria of the opercular area and microcephalia). The prognosis is determined by medical care, epilepsy management, and rehabilitation. Pediatricians should be aware of WDS clinical polymorphism. The knowledge base is upgraded annually.

   

About the authors:

Lyudmila M. Shchugareva — Dr. Sc. (Med.), professor of the Department of Children’s Neuropathology and Neurosurgery, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; Head of the Department of Neurology, Children’s City Hospital No. 1; 14, Avangardnaya str., St. Petersburg, 198205, Russian Federation; ORCID iD 0000-0002-2447-3174.

Oksana V. Poteshkina — C. Sc. (Med.), associate professor of the Department of Children’s Neuropathology and Neurosurgery, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; neurologist, Children’s City Hospital No. 1; 14, Avangardnaya str., St. Petersburg, 198205, Russian Federation; ORCID iD 0000-0001-9569-0793.

Valeriya D. Petrova —  resident of Children's City Hospital No. 1; 14, Avangardnaya str., St. Petersburg, 198205, Russian Federation; ORCID iD 0000-0002-6304-8074.

Pavel A. Salamanov — resident of Children's City Hospital No. 1; 14, Avangardnaya str., St. Petersburg, 198205, Russian Federation; ORCID iD 0000-0002-6879-6573.

Contact information: Oksana V. Poteshkina, e-mail: ovpoteshkina@gmail.com.

Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. 

There is no conflict of interests.

Received 21.09.2021.

Revised 14.10.2021.

Accepted 10.11.2021.



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