hereditary neuropathy with liability to pressure palsies - peripheral neuropathy -
nerve conduction study - pain
neuropatia hereditária com susceptibilidade à pressão - neuropatia periférica - estudos
da condução nervosa - dor
The hereditary neuropathy with liability to pressure palsies (HNPP) is an autossomal
dominant disorder characterized by recurrent sensory and motor mononeuropathies that
tend to occur at entrapment sites, although occasional patients present a generalized
neuropathy[1]
,
[2]
,
[3]. Most cases of HNPP are associated to PMP22 gene deletion[4]. Point mutations in the same gene occasionally cause HNPP and at least 26 small
mutations have been found[5]. The same region is duplicated in Charcot–Marie–Tooth disease type 1A (CMT1A)[6], the most frequent inherited neuropathy.
In contrast to CMT1A, in which nerve conduction slowing is uniform along the entire
nerve length[5]
,
[7]
,
[8]
,
[9], HNPP is characterized by multifocal or segmental conduction abnormalities[1]
,
[10]
,
[11]
,
[12]
,
[13], being necessary a correct distinction from other acquired and treatable neuropathies.
Diagnosis of HNPP is also important for correct prognostic evaluation and genetic
counseling.
Sporadic cases are sometimes found[3]
,
[14]. They may result from de novo mutations[3], incomplete family history, adoption, false paternity and no recognition of minor
manifestations as signs of neuropathy.
The classic phenotype is the occurrence of acute or subacute painless mononeuropathy
after minor trauma[2]
,
[14]. Patients frequently complaint of paresthesias after a short period of time in positions
that result in nerve compression. The prognosis is relatively benign and most mononeuropathies
resolve spontaneously. Severe injuries are avoided if the patient learns to protect
his nerves[15].
Atypical presentations as chronic sensory-motor polyneuropathies have been described
in young[3], adults[1]
,
[2] and seniors[11]. Around 30% of the patients have chronic symptoms such as cramps, paresthesias and
myalgia induced by exercise[11]. Pain was considered rare[2]
,
[16], but recent studies described pain in patients with upper limbs mononeuropathies[17]
,
[18] and occasionally neuropathic pain may be found[17]. Some patients present musculoskeletal pain that meet the fibromyalgia criteria,
potentially delaying diagnosis[19].
There is no consensus for the neurophysiology of HNPP. Verhagen et al.[20] proposed that the most discriminating findings (99% accuracy) were slowing of conduction
velocity (CV) of the fibular nerve from the fibula head to the ankle, slowing of the
ulnar nerve conduction at the elbow and prolongation of the distal motor latency (DML)
of at least one of the fibular nerves. Mouton et al.[2] and Gouider et al.[15] found that after 15 years of age all patients present prolonged DML and reduction
of the wrist sensory CV of the median nerve and prolongation of the DML or reduction
of the CV of at least one of the fibular nerves. Cruz-Martinez et al.[21] found that the DML of the median nerve, the sensory CV of the median nerve at the
wirst and the sensory CV of the sural nerves were abnormal in all affected individuals[21].
Guidelines to the diagnosis of HNPP were proposed by Dubourg et al.[16]: a) bilateral increase in DML of the median nerves associated with reduced CV in
median sensory nerve at the palm-wrist segment; b) at least one of the fibular nerves
should have increased DML or reduced CV; c) CV of the ulnar nerve at the elbow segment
is frequently reduced; d) CV in the lower limb nerves may be moderately reduced and
e) SNAP amplitudes may be reduced, mostly in the upper limbs. Infante et al.[3] proposed that the neurophysiological evaluation of patients suspected of having
HNPP should include the motor conduction in, at least, two anatomical sites of nerve
compression, particularly the ulnar nerve at the elbow and the study of the sural
nerve[3].
Li et al.[12] showed that there is a unique electrophysiological pattern in HNPP, characterized
by severe distal slowing in some nerves, multifocal conduction slowing at the sites
of entrapment and mildly reduced CV in other segments. Distal sensory conduction velocities
are usually diffusely abnormal. These findings were consistent with those of some
previous reports[1]
,
[2]
,
[3]
,
[10]
,
[11]
,
[22]. The distal slowing was more frequent in median and fibular nerves, more liable
to pressure palsies and repetitive trauma. Interestingly, the distal latencies to
more proximal muscles did not present slowing, a strong argument against HNPP being
a distal myelinopathy as suggested by others[1]
,
[22].
Luigetti et al.[23] proposed that HNPP should be suspected in patients with a demyelinating neuropathy
associated to carpal tunnel syndrome, plus another motor conduction abnormality (CV
of the ulnar nerve at the elbow, DML of the ulnar nerve, CV of the fibular nerve)
plus a sensory nerve conduction abnormality in a nerve not prone to compression (sural
or radial nerves). Following this criteria over a 20-year period, they genetically
confirmed the diagnosis of HNPP in more than 70% of the suspected cases.
In order to shed more light about the clinical and the electrophysiologic patterns
of HNPP we analyzed a group of our patients with the 17p11.2 deletion.
METHOD
We have included patients with HNPP carrying the 17p11.2-12 deletion regularly followed
at our institution. Those with other causes of neuropathy, including alcoholism, malnutrition,
vitamin B12 deficiency and systemic diseases, as diabetes and other endocrinopathies,
were not considered. Their records were evaluated retrospectively. Ethics approval
was obtained from the Ethics Committee at the HCFMRP-USP.
The patients were evaluated with special emphasis on the neuromuscular system. Electromyography
(EMG) evaluation was performed in 33 patients, using surface stimulation and recording
for the motor conduction studies and surface stimulation and needle recording electrodes
for sensory conduction studies. Compound muscle action potentials (CMAP) were recorded
from median, ulnar, fibular and posterior tibial nerves. The following characteristics
were studied: amplitude, motor conduction velocity (MCV), distal motor latency (DML)
and minimal F-wave latency. The following segments were studied: a) median nerve:
wrist to antecubital fossa and antecubital fossa to axilla; b) ulnar nerve: wrist
to below elbow, below to above elbow, above elbow to axilla; c) fibular nerve: ankle
to below fibular head and below to above fibular head; and d) posterior tibial nerve:
ankle to popliteal fossa.
Conduction block (CB) was defined as a 50% or greater decrease in negative peak amplitude
and area of the proximal CMAP. Focal slowing at a compression site was considered
present when a decrement ≥ 10 m/s was identified. Compound sensory nerve action potentials
(SNAP) were recorded orthodromically from median (index finger-wrist and palm-wrist)
and ulnar (fifth finger-wrist and palm-wrist) nerves and antidromically from radial
(forearm-base of the thumb), sural (midcalf-lateral malleolus) and superficial fibular
(leg-ankle) nerves. The following parameters were analyzed: SNAP amplitude, sensory
CV (SNCV), duration and morphology.
The data obtained were compared to the normative values of the Clinical Neurophysiology
Laboratory of our institution. Undetected potentials were generally classified as
abnormal. Statistical analysis was carried on with the SPSS Statistic version 17.0
software (SPSS Inc.). Means and percents were compared using the Student’s t-test
or Q-square test, and differences were considered significant at p ≤ 0.05.
RESULTS
Thirty-nine patients (21 men and 18 women), including a mother and daughter, fulfilled
our inclusion criteria. Family history was absent in 16/39 (41%). The mean age of
disease onset was 24 years (5 to 76 years), while the mean age of the first evaluation
was 32 years (6 to 77 years). The time of onset to evaluation was on average 8.2 years.
The first spontaneous complaints were localized muscular weakness in 24 patients (61%),
pain in 6 patients (15%), sensory loss in 5 (13%) and paresthesias in 4 (10%) ([Table 1]). At least one episode of acute paralysis of a specific nerve was reported by 18
patients (46%). 28 episodes of paralysis were reported, 19 in common fibular nerve,
6 in radial and ulnar nerves, respectively, and 2 in the axillary nerve. Position
related sensory symptoms were reported by 12 patients (31%) and a history of compression
or precipitant factors preceding the paralysis in 19 patients (48%), including playing
volleyball or soccer, climbing stairs, driving vehicles, prolonged time crouched,
physical effort, waking up, horse fall.
Table 1
Clinical findings in 39 hereditary neuropathy with liability to pressure palsies patients
with the PMP22 deletion.
|
Feature
|
|
|
Number of patients
|
39 (21M/18F)
|
|
Age at examination mean (range)
|
32 (6-77)
|
|
Age at onset mean (range)
|
24 (5-76)
|
|
Presenting manifestations
|
|
|
Muscle weakness
|
24 (61%)
|
|
Pain
|
6 (15%)
|
|
Sensory deficit
|
5 (13%)
|
|
Paresthesias
|
4 (11%)
|
|
Clinical features
|
|
|
Negative family history
|
16 (41%)
|
|
History of compression
|
19 (48%)
|
|
Acute nerve palsies
|
18 (46%)
|
|
Positional sensory symptoms
|
12 (31%)
|
|
Pain
|
9 (23%)
|
|
Painless manifestations
|
30 (77%)
|
|
Pes cavus
|
5 (13%)
|
|
Generalized areflexia
|
1 (2%)
|
|
Absent ankle jerks
|
8 (20%)
|
|
Distal atrophy
|
8 (20%)
|
|
Nerve thickening
|
4 (10%)
|
F: female; M: male.
Painless symptoms were reported by 30 patients (77%). In addition to the 6 patients
that complained of pain as the initial symptom, other 3 patients reported pain at
some point of their disease, triggered by physical effort (2 patients) and without
a precipitating factor (1 patient). Of the 6 patients that reported pain as initial
symptom, 3 presented a slowly progressive painful neuropathy predominantly affecting
the lower limbs in the set of a chronic sensorimotor polyneuropathy on the neurological
examination and 3 manifested pain in the set of a multiple mononeuropathy (1 patient
with slowly progressive pain in the territory of ulnar nerve; 1 patient with slowly
progressive pain in the left lower limb; 1 patient with pain in the lower limbs triggered
by the maintenance of a position for a long period of time). Pain was referred by
both, adults (7 patients) and teens (14 and 16 years old).
Pes cavus was present in 5 patients (13%), ankle jerks were absent in 8 (20%) and distal atrophy
was seen in 8 (20%). Two of the patients with atrophy had a sensorimotor polyneuropathy.
In the remaining patients with muscle atrophy there was a nerve-selective distribution,
most of times involving ulnar and/or median and/or fibular nerves. Nerve thickening
was rare (4 patients-10%).
None of our patients had peripheral facial nerve palsy. One patient presented a transient
involvement of the trigeminal nerve and other one an episodic involvement of the eyelid
branch of the oculomotor nerve.
On neurological evaluation, 26 patients (66.7%) had a multiple mononeuropathy pattern,
7 (17.9%) presented an isolated mononeuropathy, 4 (10.2%) had a chronic sensorimotor
polyneuropathy, 1 (2.6%) developed a predominant sensory polyneuropathy and 1 (2.6%)
patient developed a unilateral brachial plexopathy.
The most common clinical course was intermittent, comprising a succession of acute
attacks with complete or partial recovery (31 patients - 79.5%). These patients had
recurrent mononeuropathies, often from different nerves. Progressive evolution, with
no obvious fluctuations, was observed in 8 patients (20.5%), whose neuropathy pattern
included multiple mononeuropathy, chronic sensorimotor polyneuropathy or purely sensory
polyneuropathy on neurologic examination ([Table 2]).
Table 2
Clinical and electrophysiological patterns.
|
Clinical pattern
|
N (%)
|
|
Multiple mononeuropathy
|
26 (66.7)
|
|
Isolated mononeuropathy
|
7 (17.9)
|
|
Sensorimotor polyneuropathy
|
4 (10.2)
|
|
Sensory polyneuropathy
|
1 (2.6)
|
|
Unilateral brachial plexopathy
|
1 (2.6)
|
|
Total
|
39 (100)
|
|
|
Electrophysiological pattern
|
N (%)
|
|
|
ASMNFS
|
30 (91.0)
|
|
Single mononeuropathy
|
2 (6.0)
|
|
Brachial plexus + ASMNFS
|
1 (3.0)
|
|
Total
|
33 (100)
|
N: number of patients; ASMNFS: asymmetric sensorimotor neuropathy with focal slowing.
Nerve conduction studies were performed on 253 motor and 237 sensory nerves. Six patients
underwent EMG examination in another hospital. They have not been included in this
study. Despite the clinical presentation, nerve conduction studies showed a pattern
of sensory and motor neuropathy with focal conduction slowing in 31 patients, including
a patient with unilateral brachial plexopathy and focal conduction slowing ([Table 2]). Two patients had isolated mononeuropathy (a 13-year-old boy with radial neuropathy
with persistent CB at the arm segment and one 6 years-old boy with deep fibular neuropathy).
The most affected nerves in our patients were: motor ulnar nerve (CV slowing at the
elbow segment in 98.2% of the nerves), sensory ulnar nerve (CV slowing at the finger-wrist
segment in 89.6%), deep fibular nerve (at least one parameter of NCS abnormal in 83.0%
of the nerves, mainly DML or F wave latency or CV), sensory median nerve (CV slowing
at the finger-wrist segment in 82.8% and at the palm-wrist segment in 100%); motor
median nerve (DML prolonged out of proportion to the reduction in forearm CV in 80%
of the nerves), sural nerve (CV slowing in 61,7%) and superficial radial nerve (CV
reduction in 52.9%). ([Table 3]).
Table 3
Nerve conduction findings of 33 patients with hereditary neuropathy with liability
to pressure palsies.
|
Nerve conduction study
|
Normative value
|
N (ND)
|
Mean ± SD
|
Range
|
Abnormal (%)
|
|
Motor conduction
|
|
|
|
|
|
|
DML (ms)
|
|
|
|
|
|
|
Median
|
≤ 4.0
|
57 (0)
|
5.4 ± 2.0
|
3.2-12.0
|
80.7
|
|
Ulnar
|
≤ 3.1
|
59 (0)
|
3.5 ± 0.9
|
2.4-6.9
|
57.6
|
|
Peroneal
|
≤ 5.0
|
59 (0)
|
5.7 ± 1.5
|
2.7-8.6
|
57.6
|
|
Tibial
|
≤ 5.5
|
53 (0)
|
5.3 ± 1.9
|
3.4-12.2
|
30.2
|
|
CMAP (mV)
|
|
|
|
|
|
|
Median
|
≥ 3.8
|
57 (0)
|
8.2 ± 3.5
|
0.3-21.2
|
8.8
|
|
Ulnar
|
≥ 3.8
|
59 (0)
|
8.9 ± 2.3
|
4.2-16.0
|
0.0
|
|
Peroneal
|
≥ 2.8
|
59 (0)
|
4.7 ± 2.7
|
0.1-11.2
|
30.5
|
|
Tibial
|
≥ 3.6
|
53 (0)
|
8.5 ± 3.5
|
0.4-16.0
|
3.8
|
|
MNCV (m/s)
|
|
|
|
|
|
|
Median
|
≥ 50.0
|
56 (0)
|
50.0 ± 6.0
|
34.6-62.2
|
33.9
|
|
Ulnar (wrist-BE)
|
≥ 50.0
|
58 (0)
|
52.5 ± 6.2
|
43.4-70.0
|
35.5
|
|
Ulnar (BE-AE)
|
≥ 50.0
|
57 (0)
|
32.8 ± 9.4
|
11.5-51.9
|
98.2
|
|
Peroneal (ankle-BFH)
|
≥ 40.0
|
58 (0)
|
38.8 ± 6.7
|
21.3-61.9
|
55.1
|
|
Peroneal (BFH-AFH)
|
≥ 40.0
|
52 (0)
|
38.8 ± 8.3
|
22.4-64.3
|
44.2
|
|
Tibial
|
≥ 40.0
|
53 (0)
|
41.7 ± 7.4
|
28.1-67.8
|
35.8
|
|
F latency (ms)
|
|
|
|
|
|
|
Median
|
≤ 32.0
|
52 (0)
|
30.5 ± 5.1
|
20.6-41.8
|
34.6
|
|
Ulnar
|
≤ 33.0
|
50 (2)
|
32.0 ± 2.8
|
22.9-45.9
|
38.5
|
|
Peroneal
|
≤ 56.0
|
47 (5)
|
56.1 ± 7.9
|
41.2-71.1
|
61.5
|
|
Tibial
|
≤ 58.0
|
47 (2)
|
55.2 ± 5.6
|
43.0-64.1
|
34.7
|
|
Sensory conduction
|
|
|
|
|
|
|
SNCV (m/s)
|
|
|
|
|
|
|
Median
|
≥ 50.0
|
58 (0)
|
38.9 ± 9.7
|
16.3-53.6
|
82.8
|
|
Median P-W
|
≥ 50.0
|
33 (0)
|
34.1 ± 9.6
|
11.4-49.7
|
100.0
|
|
Ulnar
|
≥ 50.0
|
57 (1)
|
39.3 ± 8.9
|
20.8-53.5
|
89.6
|
|
Ulnar P-W
|
≥ 50.0
|
28 (1)
|
36.9 ± 6.0
|
23.4-56.3
|
89.3
|
|
Radial
|
≥ 50.0
|
34 (0)
|
46.3 ± 6.9
|
36.0-70.0
|
52.9
|
|
Sural
|
≥ 40.0
|
55 (5)
|
38.4 ± 5.1
|
28.1-57.5
|
61.7
|
|
Superficial peroneal
|
≥ 40.0
|
35 (4)
|
40.4 ± 5.3
|
27.6-56.1
|
43.6
|
|
SNAP (μV)
|
|
|
|
|
|
|
Median
|
≥ 9.0
|
58 (0)
|
12.1 ± 13.7
|
0.6-58.0
|
56.9
|
|
Ulnar
|
≥ 9.0
|
57 (1)
|
9.1 ± 7.7
|
1.0-50.0
|
58.6
|
|
Radial
|
≥ 15.0
|
34 (0)
|
24.5 ± 12.7
|
8.9-51.8
|
23.5
|
|
Sural
|
≥ 5.6
|
55 (5)
|
13.5 ± 7.4
|
2.3-42.0
|
21.7
|
|
Superficial peroneal
|
≥ 5.0
|
35 (4)
|
11.6 ± 7.3
|
2.4-26.5
|
33.3
|
DML: distal motor latency; CMAP: compound muscle action potential; MNCV: motor nerve
conduction velocity; F latency: minimal latency of F wave; SNCV: sensory nerve conduction
velocity; SNAP: sensory nerve action potential; N: number of recorded nerves; ND:
number of not detected nerves; SD: standard deviation; BE: below elbow; AE: above
elbow; BFH: below fibular head; AFH: above fibular head; PW: palm wrist segment.
The DML of the median nerve was more frequently prolonged than the DML of the ulnar
nerve (p = 0.03), fibular nerve (p = 0.03) and tibial nerve (p < 0.001). DML of the
ulnar and fibular nerves were significantly more frequently prolonged than those of
the tibial nerve (p = 0.002).
Temporal dispersion was observed in SNAP of median (4 times), ulnar (once) and sural
nerves (once), and in CMAP of the median and ulnar nerves (once), tibial posterior
and fibular nerves (4 times) inside and outside entrapment sites. CB of the ulnar
nerve at the elbow segment was observed 7 times, once in the fibular nerve at the
fibula neck and once at the leg segment and once in the radial motor nerve at spiral
groove. This last patient had a persistent CB at this site.
DISCUSSION
The characteristics of the population with HNPP we studied seem to be similar to other
studied populations[2]
,
[11]
,
[14]
,
[15]
,
[23]. In most patients, disease onset occurred in the first three decades of life, although
the extremes were quite large, ranging from 5 to 76 years old in our patients. Additionally,
the proportion between males and females approach to 1, as was seen in a population
of Brazilian patients with CMT1A that we have studied previously[9]. Some authors however found a male predominance (male/female = 4:3) and a significantly
earlier onset in men[2].
Family history was positive in only 23 cases (59%). In previous studies the percentage
of sporadic cases were variable[3]
,
[14]. This finding probably reflects the wide range of the clinical manifestations, that
may be very mild or even absent[3]
,
[10]
,
[15] and has important clinical implications as family history very frequently is not
a clue to the final diagnosis.
In 24 of the 39 patients (61.5%), the first clinical manifestation was painless muscle
weakness and at least one episode of acute nerve paralysis was reported by 18 patients.
This is the classic phenotype: a painless acute or subacute mononeuropathy[2]
,
[14]. Among the 18 patients with acute paralysis, 12 reported some precipitating factor,
what highlights the importance of environmental factors for development of the clinical
manifestations. Six patients reported pain as the initial manifestation. In only one
patient pain was associated to an episode of acute nerve paralysis. In the remaining
5 patients pain heralded a chronic neuropathy. Another 5 patients reported numbness
and another 4 mentioned paresthesias as the initial symptoms.
Apart from the 6 patients who reported pain as the initial symptom, other 3 patients
began the clinical picture with subacute or chronic muscle weakness but reported pain
at some point of their evolution. The pain manifested in these cases was neuropathic,
either focal associated to ulnar neuropathy, or affecting the lower limbs without
a recognized precipitating factor.
Pain is rarely reported in HNPP[2]
,
[16] and is considered a very uncommon in the acute episodes of nerve paralysis[2], but may be the initial manifestation of the disease[17] or a chronic component of this neuropathy[18]
,
[19]. Interestingly, it has been recently described a HNPP family due to a point mutation,
whose main manifestations were pain and paresthesias, without recurrent palsies[18]. Ours observations corroborates the importance of considering HNPP in patients presenting
pain, even in younger ages, as has happened in our population.
Cranial nerve involvement was rare in our population. We have seen a patient with
paresthesias in the territory of the trigeminal nerve and another with unilateral
transient paralysis of the eyelid branch of the oculomotor nerve. It seems that this
is the pattern in most studies[2]
,
[20]
,
[21]
,
[24]. Interestingly, we have previously described a HNPP patient that developed dysphagia[25]. Other rare manifestations in our patients were pes cavus and nerve thickening, as seems to be the case in most studies[3]
,
[15]. Clinically, most patients of our patients presented a pattern of multiple mononeuropathy
or mononeuropathy as seems to occur in most series[1]
,
[2]
,
[3]
,
[13]
,
[14]. However, 4 patients presented a chronic sensorimotor polyneuropathy and one patient
had a pure sensory polyneuropathy, both patterns are very rare in HNPP[3]
,
[11]
,
[23].
In our study, one patient had unilateral clinical and neurophysiological impairment
of the upper trunk of the brachial plexus. This is a very uncommonly referred presentation
that is more frequent in women[2] and that should be differentiated from acute brachial neuritis[26] and other plexopathies that are usually painful[27].
On nerve conduction studies, most of our patients (94.0%) presented an EMG pattern
of an asymmetric sensorimotor neuropathy with focal slowing of nerve conduction, suggesting
a mononeuritis multiplex pattern. Even the patient that clinically had a plexopathy
and 5 of our patients with mononeuropathy presented this pattern on neurophysiology,
that seems to be the rule in the literature[1]
,
[2]
,
[3]
,
[12]
,
[13]. Very occasionally, NCS shows only a mononeuropathy[2]
,
[21]
,
[23]. The patient that showed clinically a sensory polyneuropathy also presented in NCS
an asymmetric demyelinating sensory and motor neuropathy with focal slowing of the
ulnar nerves at the elbow segment and temporal dispersion of the right fibular and
tibial nerves at the leg segment.
In our patients, sensory CV slowing was a common feature, being more frequent in the
ulnar, median, sural and radial SNAP. In addition, abnormalities in sensory CV were
more frequent than those of motor CV outside the sites of compression as previously
described[3]
,
[12]. It should be stated, however, that the SNAP usually are evaluated at the proximal
regions due to technical difficulties, including physiological temporal dispersion
and phase cancelation.
On motor conduction studies, DML was proportionately more affected than CMAP amplitudes
and CV outside of sites of compression and also than F-wave latency, as previously
described[1]
,
[12]
,
[13]. The most affected DML were those of the median, ulnar and deep fibular nerves,
specially that of the median nerve, specially prone to pressure palsies and/or repetitive
trauma[12]
,
[13]. On entrapment sites, almost half of the patients (19 patients, 48%) referred some
history of compression or precipitant factor prior the beginning of the symptoms,
mainly in the fibular, ulnar and radial nerves, and less in the posterior tibial.
SNAP and CMAP amplitude reduction was not as frequent as CV abnormalities. Median
and ulnar SNAP and deep fibular nerves CMAP were the most affected, as happened in
other studies[3]
,
[20]
,
[22].
Temporal dispersion was seen in sensory (median, ulnar and sural) and motor nerves
(median, ulnar, posterior tibial and fibular) in segments susceptible to compression
and also not susceptible segments. CB were observed in ulnar, fibular and radial nerves,
being more frequent in the ulnar nerve at the elbow segment (7/57-12%). The frequencies
of CB described in previous studies vary greatly, from 6 to 22%[28].
In summary our study showed that the classical clinical presentation of HNPP is the
most frequent, but alternative presentations occur, including mononeuropathies, polyneuropathies
and painful neuropathies. Pain should not exclude HNPP diagnosis. The electrophysiological
features are much more homogeneous, characterized by a sensory and motor demyelinating
multiple mononeuropathy with focal slowing of CV. The most frequent abnormalities
on NCS were: prolonged DML of the median and ulnar nerves; CV slowing of ulnar motor
nerve CMAP at the elbow segment; prolonged distal latency, reduced CV and prolonged
minimal F-wave latency of the deep fibular nerve; reduced amplitude and CV of the
median and ulnar SNAP; and reduced CV of the sural and superficial radial nerves.
