Pure sensory deficit with crossed orocrural topography after pontine haemorrhage.

Queensland LHON family was found to harbour two mtDNA mutations, at positions 14 484 and 4160 (the second being found in this family only). Many family members were affected by a severe neurological disorder, which has not been reported in any other family with LHON until now. To date, the neurological disorder in the Queensland family seems to be related to the presence of the 4160 mutation. The 14 484 mutation is likely to be the cause of the optic neuropathy in this kindred. ' The nature of the midbrain lesion found in our patient remains hypothetical. In most cases, patients with LHON and CNS involvement are females affected by a multiple sclerosis-like illness.2 In our patient, some of the clinical features (global paralysis of gaze, tinnitus), MRI, BAEP, and CSF findings do not support the diagnosis of multiple sclerosis. Involvement of the CNS can occur in drug addicts, but it has never been reported in patients that had stopped taking drugs for years. Hepatitis C infection has not been associated with this kind of brainstem lesion until now. Interestingly, a very similar lesion of the dorsal midbrain has been reported in a German patient with LHON.5 This male patient had vertical gaze ophthalmoplegia and oculopalatal myoclonus, and harboured the 3460 mtDNA mutation. The brainstem lesion also decreased on successive MRI. The clinical and MRI features shared by this patient and ours suggest the existence of a separate type of CNS involvement in LHON, characterised by clinical symptoms of brainstem involvement (in particular, supranuclear ophthalmoplegia) and a dorsal midbrain lesion on MRI.

the presence of the 4160 mutation. The 14 484 mutation is likely to be the cause of the optic neuropathy in this kindred. ' The nature of the midbrain lesion found in our patient remains hypothetical. In most cases, patients with LHON and CNS involvement are females affected by a multiple sclerosis-like illness.2 In our patient, some of the clinical features (global paralysis of gaze, tinnitus), MRI, BAEP, and CSF findings do not support the diagnosis of multiple sclerosis. Involvement of the CNS can occur in drug addicts, but it has never been reported in patients that had stopped taking drugs for years. Hepatitis C infection has not been associated with this kind of brainstem lesion until now. Interestingly, a very similar lesion of the dorsal midbrain has been reported in a German patient with LHON.5 This male patient had vertical gaze ophthalmoplegia and oculopalatal myoclonus, and harboured the 3460 mtDNA mutation. The brainstem lesion also decreased on successive MRI. The clinical and MRI features shared by this patient and ours suggest the existence of a separate type of CNS involvement in LHON, characterised by clinical symptoms of brainstem involvement (in particular, supranuclear ophthalmoplegia) and a dorsal midbrain lesion on MRI.
We are grateful to Dr Eric Meary for his help in the preparation of the manuscript. the posterior tibial nerves (findings considered compatible with Charcot-Marie-Tooth disease). Brainstem auditory evoked potentials and blink reflex studies were normal.
Nine months later, the numbness in the tongue and lips on the left side had gradually reduced, but continuous burning dysaesthesia in the right lower limb persisted. The left intraoral and perioral sensory loss had resolved; a considerable decrease in pain and temperature sensations remained in the lower abdomen and leg on the right 'de,but tactiland propral epiv (S)nlvels or haemorrhages' in the pontine tegmentum.

side bu1atl n rpicpiesna
We describe the first case of pontine stroke tions were preserved. At this time, TI and leading to pure sensory deficit with crossed T2 weighted MRI showed pronounced distribution reminiscent of the sensory pat-hypointensity in the left lateral pontine tern occurring with Wallenberg's lateral tegmentum reflecting haemosiderin deposimedullary syndrome. tion (figure, B), and no cryptic vascular mal-A 71 year old man with a history of formation was detected. hypertension and diagnosed as having What is most conspicuous in this case is Charcot-Marie-Tooth disease, suddenly the presence of trigeminal sensory changes experienced left frontal headache, vomiting, ipsilateral to the pontine haemorrhage and numbness on the left side of the tongue accompanied by abnormal sensation in the and peribuccal area, followed by a tingling contralateral lower limb. A similar crossed sensation over the right leg. On admission, sensory pattemroccurs, although not isolated there was no weakness of the limbs or ataxia, but in combination with other neurological and cranial nerve palsy was not present. dysfunction, after vascular lesions in the lat-Pain and temperature sensations were eral aspect of the pons and medulla.' It is diminished on the left side of the tongue and noticeable that our patient showed lips, and were abolished on the right side of decreased pinprick and temperature senses the body below T12. Response to tactile without impaired vibration or position stimulation and vibration was slightly dissenses in a crural distribution. This turbed on the right leg, but position sense restricted sensory deficit presumably was spared. Brain MRI performed two occurred as the result of damage to the latweeks after the onset of symptoms showed a eral side of the spinothalamic tract where the lesion of high intensity in the left pontine leg representation area is situated, whereas tegmentum on both Tl and T2 weighted sensory fibres from the arm are most mediimages (figure, A), the upper part of the ally projected.i Our patient also had dysaesmedulla being spared. The somatosensory thesia and diminished intraoral perception evoked potentials were normal on both sides of pinprick sparing facial sensation. The preafter median nerve stimulation, and showed sent case is consistent with the clinical findsymmetric normal latencies with signifi-ings of Graham et a1 suggesting that the cantly reduced amplitudes when stimulating rostral spinal trigeminal nucleus in the pons 534 --------plays a major part in the perception of intraoral sensation, whereas facial sensation projects to the medullary portion of this nucleus.
As our case indicates, a small lesion at the lateral pontine tegmentum can cause a pure and crossed orocrural sensory deficit, by involvement of the rostral spinal trigeminal nucleus and the lateral side of the spinothalamic tract, where the respective sensory fibres from the mouth and the lower part of the body are immediately adjacent (figure, C).  NeurologD, 1988;38: 1529-33. Hereditary neuropathy with liability to pressure palsies with a partial deletion of the region often duplicated in Charcot-Marie-Tooth disease, type IA Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterised by recurrent peripheral nerve palsies, paraesthesiae, and less often by a prominent symmetric polyneuropathy. Nerve biopsies show thickenings of myelin called tomaculae. Chance et all found such patients to have a large chromosomal deletion located in the same region as in Charcot-Marie-Tooth disease (CMT) neuropathy, type lA. This region contains a gene for peripheral myelin protein 22 (PMP22). The role of this gene in the pathogenesis of HNPP has been shown by the discovery of a frame shift mutation creating a null mutation and resulting in the HNPP phenotype.' In the case of deletion/ duplication, a gene dosage effect has been proposed. ' In a family affected with HNPP, we found a deletion at locus D17S122 including the PMP22 gene and sparing distal loci (D17S61 and D17SI25), hence confirming the expectation that deletion of a smaller region than that previously described, but including PMP22, is capable of causing HNPP, and therefore supporting the role of PMP22 in HNPP. Patient I.1 developed leg weakness at the age of 30. Since the age of 26, he had noticed episodes of paraesthesiae on multiple nerve trunks, at first transient, then lasting and needing several surgical decompressions. At the age of 58, he had bilateral pes cavus, distal weakness, severe muscle atrophy, and areflexia in the lower limbs with transient paraesthesiae and cramps; sensory examination showed hypoaesthesia in the left per-~: only muscle atrophy and mild weakness of interosseous muscles were noted. All tendon reflexes were absent. Motor nerve conduction velocities (MNCVs) were severely slowed in median nerves (42 m/s on the right and 40 m/s on the left) and radically altered in the ulnar nerves (32 m/s on the right and 24 m/s on the left at the elbow). A nerve biopsy showed severe loss of myelinated (A) Hybridisation profiles obtained with probes positioned in the region often deleted in HNPP (loci Dl 7S122, Dl 7S61, and Dl 7S125) and with a control probe localised telomerically outside this region (locus D1 7S124). Probe p VA W409R3a detected three alleles with sizes of 2-8, 2-7, and 1 9 kbfor locus D1 7S122, probe pEW401HE detected two alleles with sizes of 5-5 and 4-4 kb at locus D17S61, and probe pVA W412R3HEc detected two alleles with sizes of 2-6 and 1 7 + 0 7 kb for locus Dl 7S125. Lane 1, unaffected homozygotic control; lanes 2 and 3, patients; lane 4 unaffected heterozygotic control. Probe pVAW409R3a (D17S122) did not detect 1 *9 kb alleles. Both alleles of locus Dl 7S61 and Dl 7S125 are present in patient II. 1. A correct familial relation was proved with VNTR probes. The presence of one allele in locus Dl 7S122 was proved by densitometric comparison of the 2*7 kb fragment with fragment 10 5 kb of the external control (Dl 7S124). (B) Eagl Southern blot hybridised with the CMTIA-REP probe pNEA102. The lanes contain the DNA of a normal subject, a CMT1A patient with the 1-5 Mb duplication, a patient with HNPP with the 1*5 Mb deletion, and the patient with HNPP (patient II. 1). Patients with HNPP with a 1*5 Mb deletion show a 370 kb junction fragment. No such fragment was found in patient II. 1. The 270 and 220 kb fragments are from normal chromosomes and 150 kb is a junction fragment specific for CMT JA patients with a 1-5 Mb duplication fibres, some having an overthin myelin sheet. Rare onion bulbs were present. Tomaculae were found in 7% of the 300 intemodes studied on teased fibres.
His daughter (patient I.1), had presented since the age of 26 with paraesthesiae and episodes of weakness of one or two weeks' duration in the peroneal, ulnar, or median nerve territories. At the age of 27, she had pes cavus, severe peroneal muscle atrophy, weakness, and distal extralemniscal and partially lemniscal sensory impairment in the lower limbs. Mild sensory impairment was noticed in the left ulnar and median nerve distribution. Tendon reflexes were all absent. In the upper limbs, MNCVs were normal in 1990, but in 1995 a bilateral entrapment of the ulnar nerve at the elbow and a left carpal tunnel syndrome were present. Semithin cross sections of the sural nerve showed a slightly reduced large myelinated fibre density, tomaculae, and lesions of remyelination. All the teased fibres presented features of tomaculae and of demyelination and remyelination. Tomaculae were found in 39% of the intemodes.
Molecular genetic studies were carried out for both patients by southern blotting analysis (figure, A) and pulsed field gel electrophoresis (PFGE) (figure, B).
Probe pVAW409R3a (D17S122) disclosed only one band for both patients whereas probes pEW401HE (D17S61) and pVAW412R3HEc (D17S125) were heterozygous for the second patient. Density scanning showed the presence of a single pVAW409R3a allele in both patients, and the presence of two alleles for the other probes in the first patient. The same technique showed only one copy of the PMP22 gene in the patients (not shown).
In PFGE analysis, hybridisation of EagIdigested DNA with CMT1A-REP probes usually detects deletion and duplication junction fragments in HNPP and CMT1A patients respectively. No such junction fragments were found for our patients with HNPP.