Head tremor was more often intermittent (11,3%) than not
(5.7%). The intermittent tremors were invariably of the 'no-no'
variety and could often be induced when the patient talked or
concentrated on writing. The more persistent head tremors were
present when sitting or standing, but not where the head was
completely supported (rest), and were of a complex type with
both 'yes-yes' and 'no-no' component (either could be
predominant).
 
 Tremor of the jaw, voice, tongue and face were never seen in
isolation and were only evident in patients with quite severe
upper limb tremors. The likelihood of tremor affecting the
cranial musculature increased with the severity of upper limb
tremor. Tremor of osbicularis oculi was most obvious whilst the
eyes were closed. Tremulousness of orbicularis oris, mentalis
and masseter were most visible during normal conversation.
 
 None of the secondary cases had evidence of parkinsonian
dystonia or other neurological disease. Cogwheeling could be
palpated in four cases (7.6%) but would disappear when the
subjects relaxed fully and Froment's' sign was noted in one
other patient (1.9%). Rigidity was never apparent and arm-swing
invariably normal. Wartenberg's test was negative in every case.
 
 Children. Amongst 14 children aged under 15 years there were six
possible cases (age range 2-13 years). Four of the remaining two
had symptoms produced by tremor
 
Natural history
 
 It was typical for individuals to state that they had felt
shakes 'inside' for several months prior to developing overt
essential tremor. Later this would progres to cause an
intermittant action tremor which appeared when the affected
person was excited or fatigued, a situation that in many
instances led to that person being labelled 'nervous'.
Subsequently, the tremor would become more persistent but could
be voluntarily suppressed for short periods of time, so that
little disability occured. At this stage the postural tremor
often appeared to be jerky, with tremor arriving in flurries
that lasted for no more than a few seconds. In the younger, mild
cases, tremor was most evident for an instant when a new posture
was adopted. It could also be seen at an early stage to
interrupt slow voluntary pronation-supination movements of the
wrist. Subsequently, as tremor increased in amplitude it became
more autonomous and oscillatory. It was then more difficult to
control and caused disability. However, even with the most
severe upper limb tremors, considerable fluctuations in
amplitude were evident and at times tremor would virtually
cease, even when a posture was maintained, only to return a few
seconds later. Tremor amplitude was also significantly altered
by changes in posture, task and the general state of activity of
the individual, but could still be voluntarily suppressed, to
some extent, for short periods of time. Tremor frequency was
also observed to vary with different tasks and positions of the
arms, as has been reported elsewhere (Bain et al., 1993b).
Hunger, emotion, fatigue and temperature (e.g. hot baths)
exacerbated tremulousness.
 
Tremor severity in index and secondary cases
 
 The means and ranges for the severity of head, upper and lower
limb postural tremors are shown in Table 2, from which it can be
seen that the brunt of hereditary essential tremor falls on the
upper limbs. The severity of upper limb tremor (as assessed by
spirography and the clinical rating scale scores) worsened with
age and the duration of tremor (Table 3). However, there was no
relationship between tremor severity measured in these ways and
the age at which tremor was first noticed (age of onset) (Table
3).
 
 The severity of leg tremor amongst the index and secondary
cases was highly correlated with that in the upper limbs
(corrrelation coefficient = 0.43, P <0.001).
 
 Severity of upper limb postural tremor and tremor evident in
spirals did not significantly differ between male and female
cases or amongst those cases with a maternal rather than a
paternal mode of inheritance (Wilcoxon's rank sum test).
 
Disability and handicap in index and secondary cases
 
 All the index patients and 81% of the definite secondary cases
completed and returned the disability and handicap
questionaires. All of the index patients and the majority (79%)
of those secondary cases who returned their questionaires
documented some disability (64% of all definite secondary
cases). The relationships between the extent of disability and
the ages of the affected cases, the age at onset and duration of
tremor are shown in Table 3. Decade specific disability is shown
for all cases (inclusive and exclusive of possible cases) in
Fig. 4A. Hereditary essential tremor never produced
 
-----------------------------------------------------------
 
 
 
 Table 2 The severity of tremor in Archimedies spirals rated
from 0 (none) to 10 (most severe) and the postural tremors  of
the upper limbs, lower limbs and head which were also scored
from 0 (none) to 10 (most severe) using a clinical rating scale
 
                          Index     Affected relatives
                         patients   Excluding Including
                                    possible  possible
                                    cases     cases
 
  (i)Spiral score (0-10)
 
          Mean             3.8        2.6       2.3
          Range            0-6.5      0-5       0-5
 
 (ii)Right arm  (0-l0)
          Mean             1.7        1.1       1.0
          Range           <4.0        0.2-4.0   0.1-4.0
 
(iii)Left arm (0-10)
          Mean             1.5        1.0       0.9
          Range            0.3-4.0    0.2-4.0   0.1-4
 
 (iv)Right leg (0-10)
          Mean             0.3        0.2       0.2
          Range           <1.7       <1.0      <1.0
 
  (v)Left leg (0-10)
          Mean             0.3        0.2       0.2
          Range           <1.7       <1.3      <1.3
 
 (vi)Head     (0-10)
          Mean           Negligible  Negligible  Negligible
          Range           <0.5       <1.0      <1.0
 
 
 
----------------------------------------------------------
 
Table 3 Correlation coefficients (r-values) for the
relationships between (i) tremor severity in the right anm
(graded clinically from 0 to 10); (ii) tremor in spirals (graded
from 0 to 10); (iii) disability (%) and the patients' ages, ages
at tremor onset and tremor deviations
 
Index and definite Spiral score Right arm tremor Disability
secondary cases                    severity
 
Age                   0.49*          0.60*        0.36*
Age or tremor onset   0.05           0.23         0.07
Duration of tremor    0.49*          0.3l**       0.28***
 
__________________________________________________________
 
Significant at: *P < 0.001; **P < 0.01; ***P < 0.05. The
significance levels were not altered by the inclusion of
possible cases.
 
 
 
---------------------------------------------------------
 
disability before the age of 15 years. The frequency with which
difficulties were documented with each item on the disability
questionnaire is shown in Appendix I. The most commonly affected
tasks were those normally performed with the dominant hand
(Appendix 1). Perhaps surprisingly several patients reported
that bathing was difficult, explaining that they would become
more tremulous in a hot environment. and 30% of index patients
and 9% of secondary cases had some difficulty with stairs. There
was no significant difference in the degree of disability found
in men compared with women or among those cases who had paternal
rather than maternal inheritance (Wilcoxon's rank sum test).
 
The extent of social handicap and the various situations in
which this was experienced are shown in Table 4, Sixtie (80%) of
the index cases and 47% of those secondary cases who returned
their questionnaires (38% of all definite secondary cases)
reported that they were handicapped some way by their tremor;
generally this was because of both physical impairment and
embarrassment rather than either factor alone. Five (25%) of the
index patients and 12% of the definite secondary cases had been
forced to change jobs or take early retirement because of
tremor. Furthermore 12 (60%) of the index patients and 19% of
the definite secondary cases had not applied for a job or
promotion because of tremulousness. The majority (65%) of the
index patients and 33% of the definite secondary cases no longer
dined out. Decade-specific handicap is shown for all cases
(including and excluding possibles) in Fig. 4B. Fifty percent of
cases were handicapped by the fifth decade and 80% by the sixth.
The subsequent decline is probably caused by the social
consequences of retirement.
 
Clinical associations
 
 The conditions affecting two or more index and definite
secondary cases are reported in Table 5A and the number of
families in which co-segregation was observed between hereditary
essential tremor and either classical migraine (migraine
associated  with  transient  focal  neurological symptoms) or
the restless legs syndrome or hypertension are shown in Table 5B.
 
 Alcohol responsiveness and effect of treatment
 
Eleven of the index patients (55%) and 25 (47.2%) of these
(definite) secondary cases reported that drinking between
 
-----------------------------------------------------------
 
Table 4 The impact of hereditary essential tremor upon
livelihood and social behaviour (handicap)
 
 Index  Reason for handicap  Secondary  Reason for handicap
 cases                        cases*
 
          E   P   E+P                      E    P     E+P
   --    --  -    ---                     --    -     ---
(a)     Percentage forced to change job/retire
   25    -   -    -             12         -    -      12
(b)     Percentage not to apply for a job/promotion
   60    20  5    35            19         5    5       9
(c)     Percentage no longer shopping alone
   55    15  5    35             7         0    2       5
(d)     Percentage no longer eating out
   65    10  0    55            33        16    5      12
(e)     Percentage no longer attending parties
   50     0  0    50            23        12    2       9
(f)     Percentage no longer able to practise their favourite
        sport/hobby
   30     5  15   10            19         7    7       5
(g)     Percentage no longer travelling by public transport
   35    10  15   10             7         0    0       7
(h)     Percentage no longer driving a car
   20     0  10   10             7         0    2       5
(i)     Percentage no longer going on holiday
   35    10   5   20             7         5    0       2
 
*Of those definite secondary canes who returned completed
questionnaires (81.1% of all definite secondary cases). Handicap
caused by: P = physical impairment; E = embarrassment; P+E =
both physical impairment and embarrassment.
 
----------------------------------------------------------
 
-----------------------------------------------------------
 
Table 5 Possible clinical associations with hereditary essential
tremor
 
(A) Conditions affecting two or more index or definite secondary
cases
 
                                        No.    Percentage
                                     affected  affected
classic migraine                        19        26.0
Left handedness                          9        12.3
Hypertension                             8        11.0
Non-insulin dependent diabetes mellites  4         5.5
Restless legs syndrome                   3         4.1
Osteoarthritis                           3         4.1
Cataracts                                2         2.7
Duodenal ulcers                          2         2.7
 
(B) Conditions co-segregating with essential tremor within one
or more kindreds
                        No. of families   Co-segregation ratio
                        co-segregating
                                           Affected* Unaffected^
 
Classical migraine             3           0.67(10/15) 0.0 (0/8)
Restless leg syndrome          1           1.0 (2/2)   0.0 (0/6)
Hypertension                   1           1.0 (3/3)   0.0 (0/0)
 
*The ratio of the number of cases with either migraine, restless
leg syndrome or hypertension who also have tremor divided by (be
total number of kin definitely affected by tremor (affected); ^
the ratio of thc number of cases who have one of these three
conditions but do not have tremor divided by the total number of
atremulous kin (unaffected).
 
-----------------------------------------------------------
and four units of alcohol would virtually abolish their tremor
for -2-4h but the tremor would rebound and be worse the
following day. In spite and because of the transient nature
response two index patients (10%) and two secondary cases (4%)
admitted to being dependent upon alcohol and would not go out of
the house without a drink. Four other
index cases and 10 secondary cases did not benefit from alcohol
and five further index cases and 18 secondary cases did not
drink.
 
 The degree of homogeneity or heterogeneity of the responses to
alcohol within the kindreds was variable. (i) amongst the
families of the 11 index patients who were alcohol responsive,
all affected relatives were alcohol responsive in nine of the
kindreds; in one kindred the effect of alcohol on the other
affected members of the family was not known; and in one family
responders and non-responders coexisted; (ii) amongst the
families of the four unresponsive index patients, two kindreds
were homogeneously unresponsive and two families exhibited
heterogeneity; (iii) amongst the families of the five index
patients in whom the response to alcohol was not known, three
were homogeneously responsive, one unresponsive and one included
both responders and non-responders.
 
 Thus, in summary, 15 of the families showed homogeneity and
four heterogeneity of responsiveness to alcohol (for the
remaining family the facts are not known).
 
 Twelve index patients had been prescribed propranolol of whom
seven (58%) had experienced some benefit. which varied from
modest to substantial. Three other patients (15%) were taking
primidone with good results.
 
 Only four affected relatives (8%) had received any treatment
for their tremor-two responding to propranolol and two to
primidone.
 
Adverse effects of drugs
 
 Three cases with long-standing postural tremor had been
prescribed prochlorperazine for unrelated symptoms. In each case
tremor severity was greatly exacerbated and this effect was
evident within days of taking the drug. Two of these cases also
developed a marked upper limb rest component to their tremor;
this disappeared when prochlorperazine was withdrawn but in both
cases a degree of cogwheeling was evident 1 year after the drug
had been stopped.
 
Biological fitness
 
 The mean number of children born to the index patients was 2.10
(SD +/-2.17) and was 2.63 (SD +/-2.12) if only index patients
over 35 years old were included. These figures are similar to
general population data in the United Kingdom (Office of
Population Censuses and Surveys 1984,1987).
 
Segregation analysis
 
 The proportions of affected to unaffected siblings of index
patients and offspring of index patients and their affected
relatives are shown in Table 6. The null hypothesis that the
actual proportions of affected to unaffected relatives would not
differ from the expected ratio of 1:1 was tested using the
formula given by Roberts and Fensbrey (1978) which includes
Yates' correction. The actual proportions did not significantly
differ from 1:1, irrespective of whether possible cases were
considered to be affected (X2 = 0.387,
P > 0.05) or unaffected (X2 = 0.688, P > 0.05).
 
 A plot of the ages at tremor onset for the index patients
versus that of their (definitely) affected relatives showed that
both young and late onset index cases had relatives with both
young and late onset tremors (Fig. 5). There was a slight trend
for individuals within the same family to have a similar age of
onset but this did not reach statistical significance {Spearman
correlation coefficients: 0.22 (excluding) and 0.17 (including
possible cases), P > 0.05].
 
Genetic counselling
 
 The risks of a currently unaffected child of a parent with
hereditary essential tremor developing essential tremor
disability or handicap are shown in Table 7. The risk of
developing hereditary essential tremor after the ages of 10 and
50 years are <20 and <6%, respectively.
 
Discussion
 
 The purpose of this study was to delineate the clinical
features of hereditary essential tremor. We approached this by
selecting 20 index patients with incontrovertible hereditary
essential tremor and then examining their relatives so as to
define the phenotype of the gene or genes involved.
 
Relationship to other neurological diseases
 
 We did not find any dystonia amongst our subjects. Several
previous studies have included patients with abnormal dystonic
postures under an expansive definition of 'essential tremor'
(Critchley, 1949, 1972; Hornabrook and Nagurney, 1976)
 
-----------------------------------------------------------
 
Table 7 Data for giving generic counselling to an apparently
unaffected child who has a parent with hereditary essential
tremor
 
Age      Risk of         Approximate percentage risk of developing a
of      developing       tremor (T),disability(D)or handicap (H)
child    tremor (%)      by the ages of
(years)
 
                  20 years       30 years    40 years      60 years
 
                   T  D  H        T  D  H     T  D  H      T  D  H
 
0         46       30 18 9      33 19 13      40 34 17     45 44 38
5         41-42    24 14 7      27 16 11      35 30 15     40 40 34
10        38-39    20 12 6      24 14 11      32 28 13     37 37 32
15        28-29     8  5 2      12  7  5      21 19  9     27 27 23
20        22-23                  4  3  2      14 10  6     20 20 18
25        19-20                               11 12  5     17 17 15
30        18-19                               11 12  5     17 17 15
35        15-17                                7  8  3     13 13 11
40         9-1l                                             7  7  6
45         7-9                                              6  6  5
50         5-6                                              3  3  3
55         3-5                                              0  0  0
60         0
 
 For example, at birth (0 years), (the risk of ever developing
hereditary essential tremor is 46%; the risks of that individual
having tremor, being disabled by it, or handicapped by it, by
the age of 20 years are 30,18 and 9%, respectively.
 
-----------------------------------------------------------
 
Rajput et al., 1984; Martinelli et al., 1987; Lou and Jakovic,
1991). In one of these studies, Lou and Jankovic (1991) reported
that amongst 350 patients diagnosed as having 'essential
tremor', 47% had dystonic posturing, which was equally
distributed amongst their familial and sporadic
cases. However, in the light of our findings and the
observations that patients with idiopathic and hereditary
torsion dystonia often exhibit tremor (Zeman et al., 1959;
Marsden and Harrison, 1974; Couch, 1976; Baxter and Lal, 1979;
Sheehy and Marsden, 1982; Fletcher et al., 1990, 1991) it would
appear that these accounts of 'essential tremor', in fact,
describe at least two separate diseases. Similarly, the absence
of nystagmus or other cerebellar signs in our subjects suggests
that papers including patients with these features (Nettleship,
1911; van Bogaert and de Savitsch. 1937; Critchley, 1949, 1972)
were not describing a single entity. Furthermore, there were no
cases of Parkinson's disease or signs of peripheral neuropathy
amongst our kindreds. Evidently, much of the previous literature
on 'essential tremor' was describing several diseases in which
postural tremor occurred and resembled that seen in hereditary
essential tremor.
 
The clinical characteristics of hereditary essential tremor
 
 The median age of onset was 15 years for our index patients and
between 14.5 and 15 years for the secondary cases (Table 1).
which is in accordance with the descriptive findings of
Critchley (1949) and Jager and King (1955). However, the actual
age of onset is likely to precede the reported date which would
tend to shift the true cumulative age of onset plot to the left
(Fig. 2). The distributions of ages at tremor onset of the index
patients and secondary cases were bimodal (Figs I and 3,
respectively), as has been found in a previous study
(Gerstenbrand et al., 1982), which might suggest that two
abnormal genes might be involved. However, the 'late onset'
(over 35 years) index cases had affected relatives with early
onset tremors and there was no tendency for late onset cases to
cluster within particular families (Fig. 5). These results do
not support a two (distinct) gene hypothesis (Harris and Smith,
1947) but indicate an individual temporal variability to
expressing the phenotype.
 
 Examination of the pedigrees and segregation ratios indicated
an autosomal dominant disorder and there were no detectable
instances of reduced penetrance. Penetrance was complete by the
age of 65 years. These findings are in agreement with the
observations of Jager and King (1955), who documented a single
large pedigree in Utah through Larsson and Sjogren (1960) in
their epidemiological study of northern Sweden, except that the
latter found a mean age at tremor onset of ~50 years perhaps
because the information on ~50% of their 210 'cases' was
obtained after the patients had died.
 
 Our data (Figs 2 and 4) can be operated on with Bayesian
statistics and be used for genetic counseling (Table 7). Thus,
the risk of a clinically normal 20-year-old offspring of an
affected individual developing tremor is ~23%. The likelihood of
this offspring developing a disability or handicap due to
hereditary essential tremor before the age of 60 years (during
working life) are ~20 and 18%, respectively.
 
 The proportions of affected men and women were not
significantly different for our cases, which is in accordance
with Jager and King's (1955) description and the epidemiological
surveys conducted by Hornabrook and Nagumey (1976), Rajput et
al. (1984) and Bharucha et al. (1988) on 'essential tremor' in
their respective communities. The biological fitness of the
index patients who were over the age of 35 years and thus
considered to have completed their families was not diminished.
 
 Biary and Koller (1985) suggested that the incidence of left
handedness in patients with essential tremor (17%) was greater
than in a normal control population (8%). Our figures of 15% for
index and 11.3% for definite secondary cases provide some
support for this notion.
 
 Tremor invariably commenced in one or both of the upper limbs
of our subjects. No examples of isolated head, tongue. voice,
jaw, trunk and leg tremors were seen either in our (selected)
index patients or the secondary cases. These entities have all
been described in the literature as manifestations of essential
tremor (see Introduction), so either these 'isolated' tremors
represent rare forms of 'essential tremor' or more likely result
from other disease processes. Dystonia can produce tremor alone
(Fletcher et al., 1990). The most common type of focal dystonia
is spasmodic torticollis (Marsden and Fahn, 1982) and isolated
head (and trunk) tremor may occur as a manifestation of that
condition (Rivest and Marsden, 1990). Tremors of the jaw, face,
tongue and voice can occur in oromandibular dystonia, lingual
dystonia and spasmodic dysphonia and at least some cases of
isolated tremor at these sites may be produced by dystonia.
Isolated leg tremor suggests the diagnosis of Parkinson's
disease, particularly if a rest component is present, or primary
orthostatic tremor if it occurs on standing with a frequency of
between 14 and 16 Hz (although transient epochs of period
doubling have been recorded in this condition (Thompson et al.,
1986; Rothwell, 1989; Britton et al., l992a). Indeed, most
patients with isolated leg tremor of frequencies between 4 and 6
Hz have a reduced [18F]dopa uptake into the putamen as seen on
PET studies, a finding characteristic of Parkinson's disease
(Brooks et al., 1992). It is also conceivable that isolated leg
tremor occurs in dystonia, but our findings suggest that
hereditary essential tremor is nor a likely culprit.
 
 The onset of tremor was reported to be in 'both hands' by 80%
of the index and 83% of the secondary cases. In the remainder,
with one exception. tremor commenced in the dominant hand.
However, in all but one mild case both hands became affected and
there were no examples of prominent unilateral tremor. A severe
persistant postural tremor of one arm is more likely to be the
result of dystonia, parkinsonism or a structural lesion, than
hereditary essential tremor. A 'hemiparetic' pattern of
tremulousness was never evident in this study.
 
 In 10% of our index patients and 66% of the definite secondary
cases the upper limbs were the only sites affected, but initial
spread from the arms to the legs (35% of index and 26.4% of
secondary cases) was more commonly reported than spread directly
from the arms to the head (30% of index and 7.6% of secondary
cases). This is contrary to the opinions expressed in several
previous accounts (Critchley, 1949. 1972; Larsson and Sjogren,
1960; Marshall, 1962; Lou and Jankovic, 1991) but most of these
studies included patients with torticollis.
 
 In descending order of frequency, tremor of the legs, head,
voice, tongue, face and jaw were seen and these occurred more
often in individuals with severe postural tremor of the arms. No
true isolated truncal tremors were observed, those encountered
being invariably due to transmission of leg tremor.
 
 No rest tremors were detected whilst the subjects were
completely relaxed and in those cases where 'cogwheeling' was
palpable, it would disappear when the subjects' voluntary muscle
activation declined. Rigidity at the wrists and elbows or
reduced shoulder swing (Wartenberg's sign) were not encountered
and no 'pill-rolling' tremors were seen. We suspect that
previous reports of rigidity (Larsson and Sjogren, 1960;
Salisachs, 1978; Salisachs and Findley, 1984) and 'pill-rolling'
(Larsson and Sjogren, 1960; Hornabrook and Nagurney. 1976) in
patients with 'essential tremor' may have been due to
coincidental pathology or exposure to anti-dopaminergic drugs.
Indeed, [18F]dopa studies have demonstrated reduced uptake of
tracer into the putamen to a degree found in Parkinson's disease
in a proportion of patients (two out of 12) with sporadic
postural arm tremor (Brook et al., 1992). In contrast, putamenal
[18F]dopa was within the normal range in eight cases of
hereditary essential tremor furthermore, in a study of twins
with Parkinson's disease two co-twins with postural arm tremor
but without rigidity or bradykinesia had reduced [18F]dopa
uptake into the putamen (Burn et al., 1992). Accordingly, some
patients with postural arm tremor but no family history of
essential tremor may well have Parkinson's disease (or dystonia)
rather that essential tremor.
 
 Kinetic tremor of the upper limbs was almost ubiquitous but the
mid-movement component only achieved an amplitude comparable
with the postural component (fingers held close to the nose with
the elbows elevated) in ~25% of index and 12% of secondary
cases. A true 'intention' component, in which tremor amplitude
was greater in the terminal phase of the nose to finger test
compared with maintained posture, occurred in ~15 and ~6% of the
index and secondary cases, respectively. The tremor component
most evident in our cases was that released at the end of
movement for the first few moments of a maintained posture until
the hands were steadied. Tremor then became more apparent as the
new position was held. No dysmetria was seen and in this respect
the terminal component of hereditary essential tremor differs
from that encountered in diseases of the cerebellum or its
connections.
 
 Head tremor occurred in seven index patients (35%) and in nine
secondary cases (17.6%) but was mild (Table 2) and always much
less than that of the arms. In nine cases an intermittent
'no-no' type of tremor was evident. In the remainder, tremor was
persistant; one had a 'yes-yes', three a 'no-no' and three
'complex' tremors, in which both 'yes-yes', 'no-no' and/or
oblique movements were present. Consequently, mild or
intermittent 'no-no' tremors account for 75% of the head tremors
seen in this study, although other types, albeit of modest
severity, did occur. Significantly, Jager and King (1955)
reported only 'no-no' head tremors in their large kindred but
other authors have described 'yes-yes' head tremors to be more
frequent (Findley, 1984; Lou and Jankovic, 1991).
 
 Leg tremor was present in 45% of the index patients and ~30% of
the secondary cases. It was invariably bilateral and highly
symmetrical. The severity of postural tremor in the legs was
much less than that in the arms (Table 2) and there was a
significant correlation between the severity of postural upper
and lower limb tremor when the latter was present. However, leg
tremor was a serious problem in only two index (20%) and three
secondary (5.7%) cases, although several others had difficulty
with stairs. It differed from primary orthostatic tremor in two
respects: first, our patients were equally troubled by their leg
tremors irrespective of whether they were walking or standing;
secondly, frequencies of their leg tremors varied from 7.5 to 10
Hz.
 
Tremor severity, disability and handicap
 
 The patients' reported ages at tremor onset had no relationship
to the severity of tremor, as assessed by rating postural upper
tremors, grading spirals or patient self-reported disability
(Table 3). Hubble et al., (1989) also concluded that the
reported age at tremor onset was not related to outcome.
 
 The ages of our index patients and their affected relatives
were highly correlated with the severity of upper limb postural
tremor, the tremor present in spirals and the extent of
disability (Table 3).  Similarly, tremor duration was
significantly correlated with both measures of tremor severity
and disability (Table 3). Men and women were affected with equal
severity and experienced equal disability. The sex of an
affected parent had no influence on the tremor severity or
disability suffered by an affected child. Our results also show
a highly significant correlation between the severity of tremor
in each arm and thus a high degree of symmetry. Larsson and
Sjogren (1960) and Marshall (1962) were also of the opinion that
'essential tremor' was generally a symmetrical condition but
others have disagreed (Critchley, 1949; Biary and Koller, 1985;
Findley, 1987).
 
 Disability began in the second decade and subsequently
increased both in terms of prevalance (Fig. 4A) and degree
(Table 3) with age. There is a variable period of time from the
onset of tremor when affected individuals can usually
control or suppress their increasingly abnormal postural
tremors, so that the degree of functional impairment is limited.
However, this ability to compensate for tremor, or control it,
during specific activities wanes as tremor severity worsens, so
that a surprising number of functions become difficult to
perform (Appendix 1). All the index patients and 79.1% of the
secondary cases who responded to the questionnaire reported that
they had experienced difficulties with one or more of the items
listed in Appendix 1. However, only 34% of the definite
secondary cases had consulted a doctor about their tremor and
only 7.6% had received suitable treatment; most were sinsply
told that they were 'old' or 'nervous'.
 
 Some degree of social handicap was reported by 85% of the index
patients and 46,5% of those definite secondary cases who
returned questionnaires. Handicap began in the later half of the
second decade and increased with age reaching a peak in the
sixth decade, when 86% of cases aged between 60 and 70 years
reported that tremor was imposing some restriction on their
social activities (Fig. 4B). Even tremors of modest amplitude
caused  embarrassment and curtailed social activities (Table 4).
In view of this, it is interesting to note how few secondary
cases sought treatment, even on an 'as required' basis. In part
this may be because they perceived that the responses of the
index cases (particularly tc propranalol) were always partial
(Table 2) and associated with side-effects. This is illuminating
as several clinical trials have shown that essential tremor at
first responds impressively to propranolol, primidone or
phenobarbitone when the efficacy of these drtigs was measured by
accelerometry but long-term functional improvement is much less
easily obtained (Baruzzi et al., 1983; Larsen and Calne, 1983;
Findley and Cleeves, 1985; Koller, 1984; Koller et al., 1986)
Significantly, in a recent study, no correlation was found
between the results of accelerometry and the self-reported
disability of 20 patients with postural tremor (Bain et
al., 1993a).
 
 Two to four units of alcohol virtually abolished tremor for 2-4
h in ~50% of cases but it was invariably worse the following
day. Fifteen (75%) of the families had homogeneous responses to
alcohol; the tremors of either 100% of the      affected members of
each of these kindreds responded to   alcohol or none responded
at all. However, in four families 20%) definite heterogeneity of
alcohol responsiveness was observed within each kindred.
 
 Classical migraine proved to be the condition most commonly
associated with hereditary essential tremor occurring in 26% of
all definite cases. It is of interest that in three of the
families (15%) classical migraine and essential tremor were
inherited together with a co-segregation ratio of 10:15 (0.67)
(Table 5).
 
 
John Cottingham    "KNOWLEDGE is of two kinds: we know a subject,
                    or we know where we can find information upon it."
[log in to unmask]                   Dr. Samuel Johnson