Differentiation of hereditary spastic paraparesis from primary lateral sclerosis in sporadic adult-onset upper motor neuron syndromes.
OBJECTIVE
To study whether clinical characteristics can differentiate sporadic presentations of hereditary spastic paraparesis (HSP) from primary lateral sclerosis (PLS). Differentiation between these diseases is important for genetic counseling and prognostication.


METHODS
Case series.


METHODS
Tertiary referral center.


METHODS
One hundred four Dutch patients with an adult-onset, sporadic upper motor neuron syndrome of at least 3 years' duration. Hereditary spastic paraparesis was genetically confirmed in 14 patients (7 with SPG4 and 7 with SPG7 mutations).


RESULTS
All 14 patients with the SPG4 or SPG7 mutation had symptom onset in the legs, and 1 of the patients with the SPG7 mutation also developed symptoms in the arms. Of the other 90 patients, 78 (87%) had symptom onset in the legs. Thirty-six patients developed a PLS phenotype (bulbar region involvement), 15 had a phenotype that was difficult to classify as similar to HSP or PLS (involvement of legs and arms only), and 39 continued to have a phenotype similar to typical HSP (involvement of the legs only). Median age at onset was lower in patients with the SPG4 or SPG7 mutation (39 [range, 29-69] years), but there was considerable overlap with patients with the PLS phenotype (52 [range, 32-76] years). No differences were found in the features used by previous studies to distinguish HSP from PLS, including evidence of mild dorsal column impairment (decreased vibratory sense or abnormal leg somatosensory evoked potentials), symptoms of urinary urgency, or mild electromyographic abnormalities.


CONCLUSIONS
In most patients with a sporadic adult-onset upper motor neuron syndrome, differentiation of sporadic presentations of HSP from PLS based on clinical characteristics is unreliable and therefore depends on results of genetic testing.
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Frans
F
Brugman
Jan H
JH
Veldink
Hessel
H
Franssen
Marianne
M
de Visser
J M B Vianney
JM
de Jong
Carin G
CG
Faber
Berry H P
BH
Kremer
H Jurgen
HJ
Schelhaas
Pieter A
PA
van Doorn
Jan J G M
JJ
Verschuuren
Richard P M
RP
Bruyn
Jan B M
JB
Kuks
Wim
W
Robberecht
John H J
JH
Wokke
Leonard H
LH
van den Berg
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000175:diagnosis* / Q000235:genetics; D009460:Neurologic Examination; D010641:Phenotype; D011379:Prognosis; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics; D000074181:Spastin; D055815:Young Adult
D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; D000074181:Spastin; C400283:SPAST protein, human