Acre ,Yeitrol Scofid 1994 89- 347-352 Printed 111 Belgruni - [ I / / righrr reseried
Coovriehhr 0 Muribeuard 1994
ACTA NEUROLOGICA SCANDINAYICA
Pallido-p yrami supranuclear u
degenerat 0 .ze paresis
Najim Al-Din AS, Wriekat A, Mubaidin A, Dasouki M, Hiari M. Pallido-pyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome. Acta Neurol Scand 1994: 89: 347-352. 0 Munksgaard 1994.
An unusual neurological syndrome in an Arab family with five affected siblings, is reported. Autosomal recessive inheritance is suggested by having multiplc affected siblings born to phenotypically normal consanguineous parents. Similar to Davison's Pallido-pyramidal syndrome, they presented with the clinical signs and symptoms of severe parkinsonism as well as evidence of cortico-spinal tract disease. In addition, they had dementia and supranuclear upgaze paresis. MRI studies showed significant atrophy of the globus pallidus and the pyramids, as well as generalized brain atrophy in later stages. Therapy with levodopa resulted in significant improvement in the extrapyramidal dysfunction. We suggest that this probably represents a new syndrome which is closely related but not identical to the pallido-pyramidal syndrome.
A. S. Najim Al-Din ', A. Wriekat2, A. Mubaidin', M. Dasouki', M. Hiari2 ' Jordan University Hospital, Medical Centre, Amman, Jordan
Key words: pallido-pyramidal syndrome: Parkinson's disease; dementia: upgaze paralysis; autosomal recessive inheritance
Amir S. Najim Al-Din, Jordan University Hospital, P.O. Box 13046, Amman, Jordan
Accepted for publication September 2 1, 1993
An autosomally recessive inherited syndrome, char- acterized by paralysis agitans and pyramidal tract signs was first recognized by Davison in 1954 (1). A total of 3 families and 2 sporodic cases with the pallido-pyramidal syndrome (PPS) have been re- ported (1-3).
We report on a closely related, but not identical, syndrome in a consanguineous Jordanian family originating from a small community (Kufor-Rakeb) located in the north of the country.
Information was available on 99 members of the family (Fig. 1). There were 48 men and 51 women. Over several visits to the community 87 living fam- ily members, were examined clinically by ASN, AW and AM, five were known to have neurological symp- toms. N o new cases were discovered other than
Patients and methods
Following the identification of the proband (V-49) in November 1992, several visits to the village were made and the available members of the family were identified and examined by ASN, AW and AM.
Affected members were evaluated as in-patients. They had detailed haematologic and biochemical profiles as well as estimation for serum copper and caeruloplasmin and urinary copper excretion. All af- fected individuals had electrocardiograms, and some had MRI of the brain and electromyography and nerve conduction studies.
Fig. I . Family pedigree symbols used: O/u normal female/male; O/. affected female/male; 0/@ deceased; 010 heterozygous female/male; double bar indicates consangiuinety and arrow in- dicates proband.
Najim Al-Din et al.
originally reported by the family. All individuals in generation VI were considered to be too young to show the clinical features (less than 10 years). Those who died prior to this study were reported to have been free. The dead family members (Fig. 1) were reported to have lived in the same village commu- nity. Elderly family members (111-3 and 111-7) were interviewed and reported that none of the dead fam- ily members were known to have a similar illness. No similarly affected individuals in the same com- munity were reported.
Details of the syndrome
All affected members were normal at birth and were reported to have had normal milestones, and later had average progress at school (at least to 6th grade) until the disease onset around the age of 13 years (16, 12, 13, 12 and 12 years for V-42, V-44, V-48, V-49 and V-53, respectively).
A summary of the neurologic features is shown in Table 1. Onset of symptoms was gradual in all af- fected members. They were noted to develop vague facies and progressively become slower in all motor activities. Walking becomes slow, they become less inclined to participate in sports and it would take them longer to dress and bathe.
Within an average of 6-12 months they would stop attending school, and all, with long enough du- ration, except V-44 and V-53 (1-yr duration) dete- riorated over another 6-12 months to the point of non-productive existence. Constant drooling of
Table 1. Neurological featrures in the family with pallido-pyramidal degeneration
saliva was a major problem particularly when the disease had progressed.
No skeletal abnormalities were detected. Exami- nation of the cardiovascular system, chest and ab- domen showed no abnormalities. ECG and chest X-rays were normal in all.
Those more severely affected (V-42, V-48 and V-49) were confined to bed in a generalized flexed posture; V-42 had moderately severe flexion con- tractures of the knees. All patients had expression- less faces with varying degrees of widening of the palpebral fissures giving a staring look. Blinking was infrequent and patients had a monotonous al- most whispering speech. Intellectual functions were impossible to assess at that stage because of the grossly impaired limb functions and speech. Lack of habituation upon tapping over the bridge of the nose (Meyersons sign) was present in all.
Hypokinesia was a fairly marked feature; patients had extreme poverty of movement. Automatic habitual movements were absent, even in those less severely affected (V-44 and V-53). All possible move- ments were slow to initiate and execute. Those who were still able to walk (V-44 and V-53) walked in a shuffle, in a festinate fashion with faulty rightening reactions. Their upright posture was that of invol- untary flexion of the trunk, limbs and head. Severe lead-pipe rigidity, in all muscle groups, was a promi- nent feature. There was no tremor nor other asso- ciated involuntary movements.
Only a mild paresis of the antigravity muscles of the lower limbs was noted in V-44, V-48, V-49 and
Age Response to Number (duration years) Sex Mentation Extrapyramidal Pyramidal Ocular L-Dopa therapy
v-42 36 M Demented Severe akinesia, MRC grade Upgaze and Can stand but not (201 and rigidty 3 paraparesis covergence walk, could speak
Beedridden paralysis and feed himself Anartheric
v -44 26 M Normal Hypokinesia Mild paraparesis Upgaze and Normal walking (14) Mobile, festinate gait, convergence
loss of associated limitation movements
v-48 22 M Demented Severe akinesia Mild paraparesis Upgaze and Walked slowly, 191 and rigidty convergence festinate gait,
Bedridden limitation loss of associated Anartheric movements
15 M Mild dementia Severe akinesia Mild paraparesis Normal Almost normal (3) and rigidty
12 F Normal Hypokinesia Mild paraparesis Normal Almost normal (1) Mobile, festinate
gait, loss of associated movements
V-53, but an almost MRC grade 3 paraparesis was brisk in all patients, with extensor plantar responses. found in V-42. No muscle wasting was detected. The Evaluation of the different sensory modalities re- jaw jerk, as well as the limb myotatic reflexes, were vealed no abnormalities. Electromyography and
Fig. 2. MRI of the brain for V-49 (I) V- 48 (11) and V-42 (111) AT the ages of 19, 28 and 31 years respectively. A, Tz weighted image (trite: 2200/80) at the level of the pyramieds showing widening of the subarachnoid space in V-49 but more significant atrophy in the other two. B and C, T , weighted images (tr/te:2200/80) showing atrophy of the globus pallidurn, clostrum and insula more marked in V-48 and V-42.
Najim Al-Din et al.
motor and sensory conduction studies were per- formed in V-47 and V-53, and were normal in both, including studies of the late responses. No signifi- cant incoordination was detected.
Three patients (V-42, V-44 and V-48) had abnor- mal eye signs, however, they were unaware of any visual symptoms. Visual acuity was normal in all. The pupils were normal and the ocular media were clear in all. Fundoscopy revealed no retinal abnor- malities and the optic discs were normal. In V-44 and V-48 upgaze and convergence were limited but lost in V-42. Bells phenomenon and oculocephalic manuveurs increased the range of upward eye move- ments. Active lid retraction was noted on attempted upgaze. The rest of eye movements were normal.
Four of the 5 patients (V-42, V-44, V-48 and V-49) had MRI studies of the brain. As they had different disease duration (20, 14,9 and 3 years, respectively), and all except V-44 had severe disability (before L-dopa therapy), it was possible to view the MRI changes in different stages of the disease (Fig. 2). V-49, who had severe disability which responded, almost to full normality to L-dopa therapy; had a mild generalized atrophy. V-42 and V-48, with more dementia, pyramidal dysfunction and less dra- matic response to L-dopa; had a more prominent generalized cerebral, cerebellar and brainstem atro- phy. Furthermore, a fairly selective atrophy of the lentiform nuclei and of the pyramids (Fig. 2) was noted.
Normal laboratory investigations included haema- tological and biochemical profiles, in particular acan- thocytosis was not detected, and the serum copper, caeruloplasmin and urinary copper excretion were