Clinical spectrum of Dyke-Davidoff-Masson syndrome in the adult: an atypical presentation and review of literature

Abstract

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare condition usually diagnosed in paediatric patients with clinical features of hemiparesis, seizures, mental retardation and contralateral cerebral hemiatrophy on neuroimaging. This report follows the case of a 22-year-old man presenting with seizures and hemiatrophy and hemiparesis. On review of cases the most common neuroimaging findings were cerebral hemiatrophy (100%) followed by hemicalvarial thickening (71.4%) and hyperpneumatisation of sinuses (71.4%). Apart from our patient, all nine cases with data on epilepsy control had drug-resistant epilepsy. The onset of seizures in adulthood, block vertebra, short stature, absence of mental retardation and well-controlled epilepsy on monotherapy makes our case exceptional—even bringing to mind the possibility of a DDMS variant. This report exhaustively reviews the wide range of clinical and radiological manifestations of DDMS in the adult, thereby adding to the literature on an unusual syndrome that causes significant neurological morbidity.

Background

Initially reported in 1933 by Dyke et al,¹ the Dyke-Davidoff-Mason Syndrome (DDMS) is a rare neurological disorder usually diagnosed in the paediatric age group characterised by hemiparesis, facial asymmetry, seizures, mental retardation (MR) and associated cerebral hemiatrophy on neuroimaging.² Only 20 cases of the syndrome have been reported in the adult population. Of these, four are from one local case series.³ It is not surprising therefore that the diagnosis for DDMS can be delayed to more than 50 years after the initial manifestations.⁴

This report follows the case of a 22-year-old Filipino male presenting with seizures, left-sided hemiatrophy and weakness.

Case presentation

A 22-year-old man came to our clinic complaining of recurrent fits. His first episode occurred 3 months earlier when he had sudden involuntary extension and stiffening of his left upper extremity lasting 2 min. The following month, he had stiffening of the left upper extremity now followed by deviation of gaze to the left side and generalised tonic clonic movements of all extremities lasting for 3 min. Two more similar episodes occurred in the next 2 months with the latest one occurring a day before his consult.

Birth history showed a non-consanguineous union resulting in a full-term normal birth at home. Prior to giving birth, however, his mother had an unrecalled infection necessitating the use of unrecalled antibiotics. No perinatal complications were noted. He developed at par with age. Growing up, his parents noticed that his left side was smaller and weaker than his right. At the time of the initial consult, he had already finished a vocational course in computer programming and pursued further collegiate studies to earn a full degree in education.

On examination he was alert, oriented, following commands, with a perfect score of 30 in the mini-mental state examination. He had hemiatrophy, grade 4/5 weakness and hyper-reflexia all on the left side (see figure 1). Cranial nerve and sensory examinations were unremarkable. He had a height of 139.7 cm, falling below his expected height of 166.4 cm calculated from his midparental height.

Figure 1.

(A–C) Different views showing hemiatrophy of the patient’s left side.

He was prescribed carbamazepine 600 mg per day. Neuroimaging revealed hemiatrophy on the right cerebrum and brainstem with hemicalvarial thickening and associated polymicrogyria. His electroencephalogram was within normal limits. Spinal MRI revealed a block T7–T8 vertebra deemed to be congenital in aetiology (see figure 2). His clinical and neuroimaging features led to a diagnosis of DDMS. Bone ageing revealed mature bone structure. Endocrine hormones (thyroid stimulating hormone, free thyroxine, follicle stimulating hormone, leutinizing hormone, cortisol, adrenocorticotropic hormone) were all normal. Psychological evaluation that included the Wechsler Adult Intelligence scale, revised Slosson intelligence test and test of non-verbal intelligence revealed the absence of MR.

Figure 2.

(A–B) Axial T1-weighted MRI showing hemicalvarial thickening (white arrow) and hemiatrophy of right cerebral hemisphere. (C–E) Axial T2-weighted MRI showing volume loss on the right side of the brainstem. (F) Block vertebra (white arrowhead), T7–T8 vertebrae, with residual intervertebral disc material and exuberant spur formation abutting the thecal sac.

Outcome and follow-up

Three years after his initial consult, there is no progression of his initial deficits. His epilepsy is well controlled only having annual breakthrough seizures when he lacks sleep. He already managed to obtain his Bachelor’s degree in education.

Discussion

An early study on paediatric hemiplegia showed that imaging findings consistent with DDMS were only apparent in children with weakness manifesting prior to 3 years of age.⁵ Thus, pathologies such as cerebrovascular insults occurring during the gestational period up to 3 years of age would most likely have the highest propensity to result in DDMS. Prolonged ischaemia during this period can decrease the production of brain-derived neurotrophic factors, resulting in brain atrophy.⁶ Subsequently, structures such as the calvarium and the sinuses tend to grow inward to compensate.⁷

The 21 cases on DDMS in the adult are summarised in tables 1 and 2. In contrast to a study done on a predominantly paediatric population² that showed male sex dominance, 57.7% of cases were female. Only four cases (1, 6, 19 and 20) identified possible aetiologies for the syndrome—of these acquired cases, three are attributed to encephalitis. It is important to note that all four patients had associated epilepsy that began before 3 years of age. In contrast, both patients (18 and 21) with adult-onset seizures had no identified specific possible aetiology for DDMS. Perhaps, this is because the possible aetiologies of DDMS in the four patients, meningitis and premature birth, can cause cortical damage severe enough to create seizurogenic foci that in turn leads to an earlier onset of seizures compared with the ‘idiopathic’ group of DDMS.

Table 1.

Dyke-Davidoff-Masson syndrome: reported cases in adults

Author, patient age and sex	Seizure type and age of onset	Laterality	Mental retardation	Focal deficits	Neuroimaging modality and features	Additional information
1. Roy, et al7 42/F	Left partial motor with secondary generalisation	Right	Present	(+) Left homonymous hemianopsia	MRI	(+) Meningoencephalitis at 28 months.
	2.5 years old			(+) Left spastic hemiparesis (+) Left extensor plantar response	(+) Calvarial thickening (+) Hyperpneumatisation of sinuses and mastoid cells (+) Crossed cerebellar hemiatrophy	(+) Depression. (+) Several combinations of AEDs initially, improved later in life. Management: AED, muscle relaxant, physiotherapy.
2. Adebayo, et al6 27/F	Generalised tonic-clonic seizures	Right	Present	(+) Left homonymous hemianopsia	MRI	(+) Febrile seizure at 2 years of age.
	2 years old			(+) Left spastic hemiparesis	(+) Calvarial thickening (+) Hyperpneumati s ation of sinuses and mastoid cells	(+) Drug-resistant seizures.
				(+) Left extensor plantar response		EEG: low amplitude background over the right hemisphere and bursts of generalised sharp-and-slow wave complexes.
						Management: AED (valproic acid), physiotherapy, cognitive therapy.
3. Sarikaya, et al17 36/F	None	Left	Present, mild	(+) Right hemiparesis	CT	(+) Left frontal alopecia.
					(+) Basal ganglia atrophy (+) Crossed cerebellar hemiatrophy (+) Calcifications in the lentiform nucleus	(+) Associated left Internal carotid artery (ICA) occlusion on Computed tomography angiography (CTA) and Magnetic resonance angiography (MRA).
						(+) Poor control on phenytoin, phenobarbital, carbamazepine.
						Management: AED (valproic acid and topiramate).
4. Malik, et al18 18/F	Generalised tonic-clonic seizures	Left	Present, mild	(+) Right spastic hemiparesis	CT (+) Calvarial thickening	(+) Drug-resistant seizure.
	9 months			(+) Right hyper-reflexia		Management: AED (valproic acid, topiramate), physiotherapy.
				(+) Right extensor plantar response
5. Arora, et al19 18/F	Seizures, unspecified	Right	None	(+) Facial asymmetry	MRI	Management: multiple AEDs, physiotherapy.
	4 years old			(+) Left hyper-reflexia	(+) Calvarial thickening
				(+) Left hemidystonia	(+) Hyperpneumatisation of sinuses and mastoid cells
					(+) Elevated sphenoid and petrous ridge
					(+) Encephalomalacia
6. Tasdemir, et al20 28/F	Seizures, unspecified	Right	Present	(+) Left hemiparesis	MRI	(+) Encephalitis at 1.5 years of age.
	1.5 years old				(+) Crossed cerebellar hemiatrophy (+) Encephalomalacia
7. Tasdemir, et al20 38/F	None	Left	Present	(+) Right hemiatrophy	MRI
					(+) Encephalomalacia
8. Ayas, et al21 26/M	Complex partial seizures	Left	None	(+) Right hemiparesis	MRI
	10 years old			(+) Right hemiatrophy	(+) Hyperpneumatisation of sinuses and mastoid cells
				(+) Facial asymmetry	(+) Brainstem atrophy
9. Ayas, et al21 28/F	Generalised tonic-clonic seizures	Left	Present	(+) Right hemiparesis	CT	(+) Drug-resistant seizures.
	<1 year old			(+) Facial asymmetry	(+) Basal ganglia atrophy
					(+) Hyperpneumatisation of sinuses and mastoid cells
10. Ayas, et al21 83/M	None	Right	None	(+) Left hemiparesis	CT	(+) Presented with history of fall.
				(+) Facial asymmetry	(+) Basal ganglia atrophy
					(+) Calvarial thickening
					(+) Hyperpneumatisation of sinuses and mastoid cells
					(+) Brainstem atrophy
11. Ayas, et al21	Generalised tonic-clonic Seizures	Right	Present	(+) Left hemiparesis	CT
44/M	7 years old				(+) Basal ganglia atrophy
					(+) Hyperpneumatisation of sinuses and mastoid cells
					(+) Brainstem atrophy
12. Ayas, et al21	Complex partial seizure	Left	None	(+) Right hemiparesis	MRI	(+) Drug-resistant seizures.
31/M	8 years			(+) Facial asymmetry	(+) Basal ganglia atrophy
					(+) Calvarial thickening
					(+) Hyperpneumatisation of sinuses and mastoid cells
13. Ayas, et al21	Generalised tonic-clonic seizures	Left	None	(+) Right hemiparesis	MRI
46/F	12 years old			(+) Facial asymmetry	(+) Basal ganglia atrophy
					(+) Calvarial thickening
					(+) Hyperpneumatisation of sinuses and mastoid cells
14. Ayas, et al21	Generalised tonic-clonic Seizures	Right	None	(+) Left hemiparesis	CT
64/F	13 years old				(+) Calvarial thickening
					(+) Hyperpneumatisation of sinuses and mastoid cells
15. Jain, et al22	Generalised tonic-clonic seizures	Right	Present, mild	(+) Left hemiparesis	CT	(+) Drug-resistant seizures (phenytoin, phenobarbitone).
30/F	5 years old			(+) Left plantar extensor response	(+) Calvarial thickening (+) Hyperpneumati s ation of sinuses and mastoid cells (+) Crossed cerebellar hemiatrophy	EEG: Poorly organised background activity of bursts of generalised spike and wave discharged admixed with low and high voltage slow waveforms.
						Management: AED (valproic acid, levetiracetam).
16. Biçici et al4	Unknown	Left	Unknown	(+) Right hemiparesis	MRI
54/M				(+) Right hyper-reflexia	(+) Calvarial thickening
				(+) Facial asymmetry	(+) Hyperpneumatisation of sinuses and mastoid cells
17. Sia and Astejada3	Generalised tonic-clonic seizures	Left	Unknown	(+) Right hemiparesis	CT	(+) Brother with a similar condition (#18).
70/M	29 years old			(+) Right hemiatrophy	(+) Calvarial thickening	EEG: diffuse slowing.
Filipino					(+) Hyperpneumatisation of sinuses	Management: poor response to AED (phenytoin).
18. Sia and Astejada3	Generalised tonic-clonic seizures	Left	Present	(+) Right spastic hemiparesis	CT	(+) Brother with a similar condition (#17).
51/M	5 months old			(+) Right hyper-reflexia	(+) Calvarial thickening (+) Hyperpneumati s ation of sinuses	EEG: mild diffuse left hemispheric dysfunction with multifocal and independent epileptiform discharges over the left temporal and right parietotemporal regions.
Filipino
19. Sia and Astejada3	Seizures unspecified	Right	Unknown	(+) Left hemiatrophy	CT	(+) Premature birth at 8 months of gestation due to a motor vehicular crash.
20/M	3 years old			(+) Left spastic hemiparesis	(+) Calvarial thickening	EEG: slowing of background activity more on the right with sharp wave discharges on both hemispheres.
Filipino
20. Sia and Astejada3	None	Right	Present	(+) Left spastic hemiparesis	CT	(+) Meningitis at 1 year of age.
39/F					(+) Calvarial thickening
Filipina					(+) Hyperpneumatisation of sinuses
21. Our patient	Focal motor seizures evolving to generalised tonic-clonic seizures	Right	None	(+) Left hemiatrophy	MRI	(+) Block vertebra.
25/M	22 years old			(+) Left hemiparesis	(+) Calvarial thickening	(+) Short stature.
					(+) Crossed cerebellar hemiatrophy	Seizures responsive to single AED.
					(+) Polymicrogyria, right	Management: AED (carbamazepine).

AED, antiepileptic drug; EEG, electroencephalogram.

Table 2.

Summary characteristics of 21 cases of adult diagnosis of Dyke-Davidoff-Masson syndrome

Mean age at diagnosis (years)	39.0±18 (range: 18–83)
Sex: % Female	57.70%
Mean age of seizure onset (years)	6.7±8.2 (range: 0.52–29)
Laterality: % Right	52.40%

Of those with seizures (76.1%), the onset of fits was during childhood except for our patient and 17. Peculiar presentations included hemianopia (Cases 1 and 2) and hemidystonia for case 5. It is also worthwhile to note that the series of Sia featured two brothers, (Cases 17 and 18) bringing to mind a possible genetic cause of the syndrome.³

MR is only present in 61.1% of the reviewed cases. Among patients with data on seizures and MR, it is worthwhile to note that all patients with seizures before 3 years of age (Cases 1, 2, 4, 6, 9 and 18) had MR while those with seizure onset after 3 years of age (Cases 5, 8, 11, 12, 13, 14, 15 and 21) only 2 (Cases 11 and 15) had MR. This suggests that patients with both epilepsy and MR have earlier onset of seizures

Unilateral weakness was a consistent finding. Imaging showed cerebral hemiatrophy in all—even involving the brainstem in five cases. (Cases 8, 9, 10, 11 and 21) Hemicalvarial thickening and hyperpneumatisation of sinuses with 15 patients each were the second most common neuroimaging findings. Polymicrogyria was only seen in our patient but a previous report of DDMS with the same feature has been reported in two cases in the paediatric population.^{8 9} In stark contrast to our patient, all other cases with data on epilepsy control showed patients on multiple antiepileptic drugs (AEDs) with difficult to control seizures. (Cases 1, 2, 3, 4, 5, 9, 12, 15, 17) All cases with data on therapy were managed with AEDs and physiotherapy only. Hemispherectomy for a paediatric DDMS patient with drug resistant epilepsy and hemiparesis resulted in seizure freedom.¹⁰ Despite the patient having adult onset seizures, it is important to emphasise that he already had features consistent with DDMS even in childhood, that of unilateral weakness and atrophy.

Seizures and hemiatrophy is consistent with Rasmussen’s encephalitis; however, the lack of progression in the patient’s deficits make this diagnosis unlikely.¹¹ The Russel-Silver syndrome with associated short stature and hemiatrophy of limbs is a close differential but the neuroimaging findings of our patient are not consistent with this condition.¹²

A new syndrome aptly named ‘unilateral cerebral polymicrogyria with hemiatrophy’ (UCPH) is the closest differential for the case accounting for most of our patient’s symptoms and neuroimaging findings. The syndrome first came to light in a case series of 12 children with neuroimaging features for which the syndrome was named after.¹³ After a review of the 35 reported cases, three key points make UCPH a less likely diagnosis for our patent.^13–16

1. None of the reported cases of UCPH have hemicalvarial thickening—a neuroimaging feature present in our patient.

2. Unlike our patient, all the patients with UCPH had onset of seizures in the paediatric age group.

3. All the patients with UCPH with data on their intelligence were found to have some degree of MR; in contrast, our patient was found to have normal intelligence after testing with a battery of psychological evaluations.

Because of these, DDMS is still the most likely diagnosis for our patient.

This review of DDMS cases showcases the gamut of clinical and radiological findings that accompany this syndrome. Absence of MR in 61.1% of adult cases suggests that MR may not be a necessary criteria for the diagnosis of DDMS and that DDMS may be a spectrum with less severe cases recognised later in life during adulthood. The absence of MR, adult onset of seizures, block vertebra, short stature and epilepsy, controlled on monotherapy makes our case exceptional—even bringing to mind a possible variant of DDMS. With majority of patients in the review having drug-resistant epilepsy, epilepsy surgery may be an underutilised treatment option. This report on DDMS in the adult, adds to the literature on a rare neurological syndrome that can significantly impact the patients’ quality of life.

Patient’s perspective.

In the vernacular (Filipino)

Epilepsy, nung una, hindi ako maniwala na magkakaroon ako nito. Wala naman kasi sa pamilya ko ang meron nito or nagkaroon nito. Ako lang. Nung nagkaroon ako marami akong natutunan. Paano dapat alagaan ang sarili at hindi dapat istress ang sarili. Siguro ang tanging tanong ko lang ay kung gagaling ba ako? Liftime sickness daw kasi ang epilepsy. Natuto ako maging disiplinado at huwag abusuhin ang sarili.

Nung una ayoko inumin ang gamot ko sa epilepsy, na carbamazepine dahil nagkakaroon ako ng hilo. Hindi ako makatayo or makaupo ng maayos or kahit sa paglalakad. Pero nung naglaon okay na ako.

Nasanay na at patuloy na nag-iingat na wag ako atakihin ng sakit ko.

Translated (English)

Epilepsy, at first I could not believe that I was diagnosed with the disease. No one in our family has epilepsy—just me. I learned a lot having this disease—how to take care of myself and avoid stress. I would just like to ask if I will ever be cured of the disease? I learned that epilepsy can be a lifetime sickness. I learned how to be disciplined and to not overexert myself.

At first, I did not want to drink my medicine, carbamazepine because it caused vertigo. I couldn’t sit, stand or walk properly. But eventually the dizziness disappeared and I felt better. I have gotten used to my disease. I take measures to ensure that my seizures do not recur.

Learning points.

• The Dyke-Davidoff-Mason Syndrome (DDMS) can also present in adulthood with findings that are variations of the classically described clinical and neuroimaging findings of DDMS.

• Absence of MR in 61.1% of adult cases suggests that MR may not be a necessary criteria for the diagnosis of DDMS.

• The absence of MR, adult onset of seizures, block vertebra, short stature and epilepsy, controlled on monotherapy makes our case exceptional.

• Epilepsy surgery may be an underutilised treatment option for DDMS.