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Background Up to 33% of the general population over 50 years of age are affected by nocturnal leg cramps. Currently there are no generally accepted clinical characteristics, which identify nocturnal leg cramps. This study aims to identify these clinical characteristics and to differentiate between them and the characteristics of restless leg syndrome and periodic limb disorder. MethodA systematic literature study was executed from December 2015 to May 2016. This study comprised of a systematic literature review of randomized clinical trials, observational studies on nocturnal and rest cramps of legs and other muscles, and other systematic and narrative reviews. Two researchers independently extracted literature data and analyzed this using a standardized reviewing protocol. Modified versions of the Cochrane Collaboration tools assessed the risk of bias. A Delphi study was conducted to assess agreement on the characteristics of nocturnal leg cramps. ResultsAfter systematic and manual searches, eight randomized trials and ten observational studies were included. On the basis of these we identified seven diagnostic characteristics of nocturnal leg cramps: intense pain, period of duration from seconds to maximum 10 minutes, location in calf or foot, location seldom in thigh or hamstrings, persistent subsequent pain, sleep disruption and distress. Conclusion The seven above characteristics will enhance recognition of the condition, and help clinicians make a clear distinction between NLC and other sleep-related musculoskeletal disorder among older adults.
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R E S E A R C H A R T I C L E Open Access
Criteria in diagnosing nocturnal leg cramps:
a systematic review
Joannes Hallegraeff
, Mathieu de Greef
, Wim Krijnen
and Cees van der Schans
Background: Up to 33% of the general population over 50 years of age are affected by nocturnal leg cramps. Currently
there are no generally accepted clinical characteristics, which identify nocturnal leg cramps. This study aims to identify
these clinical characteristics and to differentiate between them and the characteristics of restless leg syndrome and
periodic limb disorder.
Method: A systematic literature study was executed from December 2015 to May 2016. This study comprised of a
systematic literature review of randomized clinical trials, observationalstudiesonnocturnalandrestcrampsoflegsand
other muscles, and other systematic and narrative reviews. Two researchers independently extracted literature data and
analyzed this using a standardized reviewing protocol. Modified versions of the Cochrane Collaboration tools assessed
the risk of bias. A Delphi study was conducted to assess agreement on the characteristics of nocturnal leg cramps.
Results: After systematic and manual searches, eight randomized trials and ten observational studies were included. On
thebasisoftheseweidentifiedsevendiagnostic characteristics of nocturnal leg cramps: intense pain, period of duration
from seconds to maximum 10 minutes, location in calf or foot, location seldom in thigh or hamstrings, persistent
subsequent pain, sleep disruption and distress.
Conclusion: The seven above characteristics will enhance recognition of the condition, and help clinicians make a clear
distinction between NLC and other sleep-related musculoskeletal disorder among older adults.
Keywords: Cramps, Nocturnal, Diagnosis, Aged, Sleep-wake transition disorder, Restless legs syndrome
Nocturnal Leg Cramps (NLC) is a musculoskeletal dis-
order characterized by suddenly occurring, episodic, per-
sistently painful, involuntary contractions of the calf,
hamstrings or foot muscles at night [1]. Up to 33% of the
general population over 50 years of age have complaints
related to NLC [2]. In 20% of these cases, cramps also
occur during rest periods in the daytime [3]. Sleep distur-
bances, which may seriously affect well-being and quality
of life, are common among patients with NLC [4, 5].
Symptoms, as well as prevalence and incidence, progress
with advancing age [1, 6]. There is no consensus about
aetiology of NLC, however it is suggested that shortened
muscle length among older less physically active people is
a risk factor [1]. Medical pathologies associated with NLC
are chronic liver and renal failure (haemodialysis), vascular
diseases, magnesium or calcium deficiency, dehydration
and varicose veins [2, 7]. A pre-stretching protocol by
physical therapists, as well as medical treatment blocking
the medial branch of the deep peroneal nerve after lumbar
surgery, may be effective in treating NLC [8, 9].
In contrast to the restless leg syndrome (RLS) and the
idiopathic periodic limb movement disorder (PLMD),
diagnosing NLC is hindered due to lack of a categorical
definition of NLC. Moreover, different types of muscular
cramps such as idiopathic, rest, leg, or pregnancy-related
cramps are similar to NLC symptoms and are often con-
fused in the literature [10].
Diagnostic criteria for RLS are clearly stated as follows:
uncomfortable and unpleasant sensations in the legs, feet
or arms associated with an urge to move; relief of symp-
toms by moving the affected limb; occurrence during rest
in the evening or at night [11, 12]. The International
* Correspondence:
Research Group Healthy Ageing, Allied Health Care and Nursing, Hanze
University of Applied Sciences, Groningen, The Netherlands
SOMT University Campus, Institute for Master Education in Musculoskeletal
Therapies, Amersfoort, The Netherlands
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International License (, which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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Hallegraeff et al. BMC Family Practice (2017) 18:29
DOI 10.1186/s12875-017-0600-x
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Restless Leg Syndrome Study Group approved the validity
of a rating scale for RLS, which reflects the severity of the
discomfort [11]. Idiopathic PLMD symptoms include the
repetitive jerking movements of the leg for approximately
20-30 seconds during sleep, with the complaints when
awake being more intense than during sleep. PLMD can
be classified into mild, moderate, and severe levels as mea-
sured by the Periodic Limb Movement Index. Additionally,
both RLS and PLMD may co-exist [12]. No consensus has
been reached regarding the diagnostic criteria for NLC, or
how to differentiate them from the RLS and PLMD criteria
[12]. Primarily based on the patient history, the diagnosis
of NLC may be confused with RLS or PLMD [1].
Generally, nocturnal pain can be a symptom of a ser-
ious pathology such as Parkinson disease, cardiovascular
and renal diseases, lumbar canal stenosis, osteroarthritis,
peripheral neuropathy or cirrhosis. It is important to
differentially diagnose NLC when is present as a nonspe-
cific musculoskeletal disorder, or related to serious
This study focuses on strengthening the available cri-
teria in order to prevent the misdiagnosis of NLC, for
RLS or PLMD. The first aim of this literature review is
to identify characteristics for diagnosing NLC. The sec-
ond aim is to differentiate these diagnostic characteris-
tics from other sleep-related disorders, such as RLS and
PLMD, for application in clinical care.
A systematic review was done to identify diagnostic criteria
of NLC. The methodology is specified in our PROSPERO-
registered protocol (16467) and conforms to Preferred
Reporting Items for Systematic Reviews and Meta-analyses
(PRISMA) guidelines [13]. In order to differentiate between
NLC, on the one hand, and RLS and PLMD, on the other,
an additional Delphi methodology was used. In this study a
focus group of 27 experts assessed the relevance of the
diagnostic criteria.
Sourcing information
An experienced librarian assisted in the development of
a search strategy to identify recognized terminology.
Four electronic databases were used including MED-
LINE, Cinahl, EMBASE and PEDro (1990 to May 2016).
The search included all commonly used terms for
NLC such as cramps,muscle cramps,nocturnal leg
cramps,leg cramps,night leg cramps,rest cramps,
sleep-wake transition disorders/classification,aged,
demiology,rehabilitation,parasomnias,clinical trial,
randomized controlled trial,observational study,clin-
ical study,systematic review,meta-analysis,validation
studyor letter.
Selection criteria
Inclusion criteria included randomised clinical trials, or
observational studies reflecting NLC, muscle cramp, leg
cramp, or rest cramp. The studies had to use the diag-
nostic criteria and classification in older adults aged over
50 years. A time frame spanning the previous 25 years.
Studies with non-English abstracts were excluded.
Two authors (JMH and MHGdG) independently ex-
tracted, screened, and reviewed all titles and abstracts of
the retrieved articles. The articles were interpreted and
classified into randomised clinical trials and observa-
tional studies. Reference lists of any recent reviews were
hand searched in order to identify additional studies and
help in excluding any duplicates.
Data extraction
The characteristics, diagnostic features and population
characteristics of the investigated populations were sum-
marised and catalogued. Randomised clinical trials and
observational studies were screened for descriptions of
diagnostic terms or classification criteria for NLC during
sleep among adults aged over 50. For each included
study, descriptive data regarding the participants and
diagnostic terms were extracted. A flowchart was made
to show the process of the literature search [13].
Quality assessment
Cochrane checklists for randomised clinical trials and
observational studies were appraised using the methodo-
logical quality (risk of bias) of the included studies. To
discuss any discrepancies between the two reviewers,
consensus meetings were arranged. Complete agreement
was reached after discussions with a third reviewer
(CvdS) in all of the cases.
Delphi sub-study
The Delphi methodology was performed to examine the
relevance of the extracted diagnostic criteria found in
the systematic review. A questionnaire with closed-
ended questions on a five-point Likert scale (always
mostly sometimes never - not known) was presented
to a focus group of experts. The questionnaire was de-
veloped based on the results of the literature search and
comprised the following items: (1) Are you known with
NLC; (2) NLC has a sudden onset; (3) NLC is only
present at night; (4) Pain and/or intense pain is the main
characteristic; (5) NLC duration varies from seconds to
10 minutes; (6) NLC location is thigh, calf or foot; (7)
After reduction of NLC there will be pain afterwards; (8)
NLC might be associated with sleep disruption; (9) NLC
is associated with medication use / comorbidity; (10)
NLC might be associated with distress. The designated
criteria for inclusion were established by more than 50%
Hallegraeff et al. BMC Family Practice (2017) 18:29 Page 2 of 9
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of the respondents. Geriatric experts were randomly
chosen on the basis of their expertise in geriatric health.
After completing the systematic search and manual
searches of the reference lists of the systematic reviews
and narrative reviews and after removing duplicates and
records not meeting the inclusion criteria, in the screen-
ing a total of 221 papers were yielded of which 162 were
irrelevant and had to be excluded due to not meeting ti-
tles and abstracts. This resulted in 59 records that were
appropriate for further evaluation. Subsequently, 41 full-
text articles were excluded because they did not describe
diagnostic criteria of NLC in older adults. No primary
studies with the focus on diagnosing were found. Eight
randomised clinical trials and ten observational studies
were eligible for analysing classification characteristics of
NLC. Full consensus between MHG and WPK was
reached regarding the included citations. Figure 1 presents
the selection of the studies through the review process.
Two randomised clinical trials [14, 15] had high and
unclear risk of bias due to a lack of internal validity,
however the description of the included NLC patients
was adequate.
The groups were treated equally in all studies, and the
randomisation procedure was performed well, except in
one instance. Among the observational studies two
showed low risk of bias [4, 16]. In all studies, the popu-
lations were well defined.
See Tables 1 and 2 for risk of bias and Table 3 for the
description of the study characteristics.
The total number of participants in the 18 included
studies was 36,515 of which the study of Garrison et al.
2015 included 31,339 participants. Overall, 51% of the
participants were male and mean age of participants was
64 years (range 51-75 years).
Comorbidities were categorized in five domains:
Fig. 1 Flow diagram of the systematic review, modified from Moher et al., 2009 [13]
Hallegraeff et al. BMC Family Practice (2017) 18:29 Page 3 of 9
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Heart and vascular diseases: coronary artery disease,
peripheral vascular disease, hypertension, varicose
veins, ankle oedema, vascular occlusive disease and
leg claudication.
Kidney diseases: renal dialysis, haemodialysis,
uraemia, hypocalcaemia and hypokalaemia.
Neurological diseases: neuropathies, motor neuron
disease, radiculopathy or hereditary cramp
syndromes, neuromuscular or neurological diseases,
peripheral neuropathy, Amyotrophic Lateral
Sclerosis, poliomyelitis, lumbar spinal radiculopathy,
lumbar canal stenosis and stroke.
Musculoskeletal disorders: arthritis and myopathies.
Metabolic disorders: Diabetes Mellitus, plasma
electrolyte abnormalities hepatic, liver cirrhosis,
postphlebitic syndrome volume depletion,
Table 1 Risk of bias of the included randomised clinical trials (9-item Cochrane checklists for randomised trials
Randomisation Concealed
Loss to
follow up
to treat
treated equaly
Connolly 1992 [29]
+- ++--+++
Coppin 2005 [5]
++ -++++++
Garrison 2011 [17]
++ +++++++
Hallegraeff 2012 [9]
++ +++++++
Jansen 1997 [18]
++ +++++++
Roffe 2002 [19]
++ ++-++++
Serrao 2001 [14]
+- ----+-+
Young 1993 [15]
-- ????-?+
Coppin 2005 [5], Garrison 2011 [17], Hallegraeff 2012 [9], Jansen 1997 [18] and Roffe 2002 [19] showed low risk of bias
Table 2 Risk of bias of the included observational studies (9-item Cochrane checklist for observational studies)
Groups well
Exposure Outcome Blinding Follow-
Loss to follow
Confounding Generalizability
Angeli 1996 [20]
Baskol 2004 [21]
Garrison 2015 [22]
Garrison 2012 [2]
Hawke 2013 [4]
Hawke 2013 [23]
Hirai 2000 [24]
Naylor 1994 [25]
Nishant 2014 [26]
Oboler 1991 [27]
Baskol 2004 [21], Garrison 2015 [22], Hawke 2013 [4] and Hawke 2013 [24] showed low risk of bias
Hallegraeff et al. BMC Family Practice (2017) 18:29 Page 4 of 9
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Table 3 Characteristics of the included studies
clinical trials
Study objective
Number of participants
Diagnostic criteria Comorbidities associated with
NLC and medication use
Connolly 1993 [29]
Efficacy of quinine
59 yrs.
Male 100%
Nocturnal leg cramps. Aged > 50.
Foot, lower part of leg, sometimes
thigh. Sleep interruption.
Coronary artery disease, Peripheral
vascular disease, Hypertension, Diabetes
Medication: diuretics
Coppin 2005 [5]
Effect of calf stretching
N= 181
75 yrs.
Male 46%
Nocturnal leg cramps, aged > 60,
painful and involuntary. Muscle
spasms. Disrupt sleep. Disruption.
Most commonly in the leg, relief
by stretching.
Renal dialysis, asthma and hypertension.
Medication: diuretics, nifedipine,
salbutamol and terbutaline
Garrison 2011 [17]
The effect of magnesium in
individuals with leg cramps
69 yrs.
Male 30%
Leg cramps, aged > 50, at rest
(bed or night). Legs and feet.
Painful muscle contractions.
Participants with comorbidities excluded
Hallegraeff 2012 [9]
Effect of pre sleep stretching
70 yrs.
Male 50%
Nocturnal leg cramps, aged > 55,
Suddenly, episodic. Involuntary.
At rest or sleep. Calf, hamstrings
or foot. Muscles are tender and
hard. Intense painful. From
seconds to minutes. Distress.
Sleep disruption. Maximum ten
Varicose veins and arthritis. Physical
inactivity and inadequate stretching and
reduced muscle and tendon length.
Medication: diuretics, lithium, steroids,
Jansen 1997 [18]
Efficacy of hydro quinine in muscle
N= 102
54 yrs.
Male 37%
Involuntary muscle contraction.
Painful Sudden onset. Muscle
hardening, maximum duration
10 minutes.
Not stated
Roffe 2002 [19]
The effect of magnesium in chronic
non-pregnant individuals
63 yrs.
Male 58%
Leg cramps. Painful contractions
of any muscle group in the leg.
Sudden onset. Successive
improvement. Palpable hardening
of the muscle. Distress.
Arthritis, peripheral vascular disease,
varicose veins, ankle oedema
Serrao 2001 [14]
To evaluate the efficacy and safety of
gabapentin in the treatment of muscle
54 yrs.
Sudden, involuntary, painful
contractions. Maximum of 10
minutes. Sleep disturbance.
Neuropathy, radiculopathy, Isaacs
syndrome, multiple sclerosis, Parkinsons
disease, vascular disease
Young 1993 [15]
The effect of naftidrofuryl in
individuals with rest cramps
61 yrs.
Male 64%
Rest cramps. Night-time cramps.
Foot, calf muscles. Distress.
Not stated
Angeli 1996 [20] To define the features, prevalence, and
pathophysiology of therapy for muscle
and small muscles cramps in cirrhotic
N= 192
56 yrs.
Male 65%
A-symmetric involuntary contractions
or stiffness in calves and feet. At rest
or at night
Cirrhosis, vascular occlusive disease,
peripheral neuropathy, diabetes mellitus,
severe renal failure and postphlebitic
Baskol 2004 [21]
The prevalence of muscle cramps in
non-alcoholic cirrhosis patients.
52 yrs.
Male 57%
Muscle cramps. Aged > 50. Involuntary.
Painful, visible contraction. Sudden
onset. At rest or sleep. From seconds
to minutes. Affects quality of life. At
least once per week. Sleep disruption.
Liver cirrhosis, diuretic, alcohol use,
volume depletion, hyponatremia,
haemodialysis, hypothyroidism, uraemia.
2015 [22]
Motor neuron disease, radiculopathy or
hereditary cramp syndromes
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hyponatremia, hypothyroidism, hyper- and
hypothyroidism and acute extracellular volume
depletion including excessive perspiration.
The analysis of 18 primary studies revealed twelve differ-
ent diagnostic criteria used: rest, sleep or night(n= 16);
painful(n= 12); aged > 50(n=8); involuntary(n= 10);
sudden onset(n=7; posterior calf, foot or thigh(n=8);
sleep disruption(n=7); persisting pain afterwards(n=4);
duration from seconds to several minutes(n=5);distress
(n=4); stiffness(n=1) and asymmetrical cramps(n=1)
Clinical classification characteristics
After counting the number of times the criteria were de-
scribed, and after comparing the twelve criteria to RLS
Table 3 Characteristics of the included studies (Continued)
Seasonally variation of symptom
burden of leg cramps in the general
N= 31.339
69 yrs.
Male 38%
Painful involuntary muscle cramps
in the legs or feet during rest. It
interrupts sleep.
Garrison 2012 [16]
Evaluating the association between
diuretics, statins and long-acting β2
agonists use.
N= 3492
69 yrs.
Male 39%
Nocturnal leg cramps. Painful legs
or feet. During rest or sleep
Medication: diuretics and long-acting β2
Hawke 2013 [4]
Impact of NLC on health related
quality of life.
N= 160
71 yrs.
Male 41%
Nocturnal leg cramps. Pain afterwards.
Sleep disruption. Aged >60 with sleep
disruption. Reduced quality of life.
Gradually lessens. Sudden, involuntary
painful contraction. At night and rest.
Relief by stretching.
Participants with comorbidities known to
cause cramp excluded
Hawke 2013 [23]
Factors associated with night-time calf
muscle cramps
N= 160
71 yrs.
Male 41%
Reduced strength dorsiflexion foot.
Distress. Lesser quality of life.
Interference of activities of daily living.
Hamstring tightness. Foot or leg coldness
Participants with comorbidities known to
cause cramp were excluded
Hirai 2000 [24]
NLC in general population and in
patients with varicose veins
N= 333
Age not stated
Male 26%
Muscle cramps. Aged >50. Intense
painful with sudden onset in calf,
foot or thigh. Maximum duration
10 minutes. At least once per week.
Varicose veins
Naylor 1994 [25]
Prevalence, severity and correlation
with vascular diseases
73 yrs.
Male 44%
Rest cramps. Aged > 50. Distress.
Less quality of life.
Peripheral vascular disease
Nishant 2014 [26]
Prevalence of nocturnal leg cramps
in LSCS patients and in general
56 yrs.
Male 53%
Nocturnal cramps. Painful. Acute
and involuntary. At sleep or rest.
Knee flexion test might be indicative
for NLC.
Amyotrophic lateral sclerosis, poliomyelitis,
peripheral neuropathy, lumbar spinal
radiculopathy; metabolic disorders including
diabetes, pregnancy, uremia, liver cirrhosis,
and hyper- and hypothyroidism; acute
extracellular volume depletion including
excessive perspiration, hemodialysis, diarrhea,
and diuretic therapy; hereditary disorder.
Hypertension, hypocalcaemia, hypokalaemia,
vascular diseases.
Medications: diuretics, antidepressants,
calcium blockers, statins, and steroid,
Oboler 1991 [27]
Prevalence and treatment regimens of
N= 262
60 yrs.
Male 95%
Painful and involuntary in the calf
with a visible palpable knot. At rest
or sleep.
Arthritis, Peripheral vascular disease,
Hypokalaemia, Coronary artery disease,
Hypertension, Kidney disease, Stroke,
Diabetes Mellitus, Hypocalcaemia.
In total 18 studies are included for analysing NLC characteristics: eight randomized clinical trials and ten observational studies
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and PLMD criteria, the following criteria were deemed
not distinctive enough: at rest or sleep,aged,involun-
tary,sudden onset,stiffnessand asymmetrical. As a re-
sult, the following seven criteria remained in order to
differentiate NLC from RLS and PLMD: pain,intense pain,
period of seconds to a maximum of 10 minutes,located in
posterior calf or foot,subsequent pain,sleep disruption
and distress. These seven classification characteristics dif-
ferentiate from RLS and PLMD See Table 4.
This review has identified seven criteria, derived from
consensus, which can be employed as a framework to
differentiate NLC from RLS or PLMD.
Distress and sleep disruption are indicated in a limited
number of studies and are associated with negative im-
pacts on physically related aspects of the quality of life
[4]. Similarly, subsequent painis also a criterion as a
consequence of the occurrence of NLC. The NLC char-
acteristics that were revealed as the most discriminatory
compared to those of RLS and PLMD include in-
tense pain with duration of a maximum of ten minutes
in the calf or the foot, with relief of the symptoms oc-
curring with no intervention. In contrast to NLC, pain
in rest or during sleep in the calf or foot can also be due
to vascular insufficiency.
In contrast to previous studies, that included all kind of
cramps in different ages, the current review focused on
NLC among older adults aging 50 years and older there-
fore excludes other types of cramps [13, 28]. Naylor et al.
1994, showed the highest prevalence of NLC is in age
group 60-69 years, which is in line with our result with a
mean age of the total population in the included studies of
64 years [25]. We also confirmed the previous findings
that vascular and renal comorbidities are the most stated
and are clinically relevant in elderly people [4, 9, 1921,
25, 27, 29]. In addition, the use of diuretics is known to
cause muscle cramps [9, 16, 21, 2426, 29]. Consequently,
we suggest that vascular and renal comorbidities as well
as the use of diuretics could be considered as correlational
factors for NLC. This may improve the accuracy of future
NLC diagnoses.
Managing the symptoms of patients with NLC can be
a challenge in daily clinical practice considering how re-
cent some developments in the diagnosis and treatment
Table 4 Involuntary musculoskeletal disorders at rest or nocturnal
with sudden onset in elderly above 50
Nocturnal leg
Restless leg
Periodic Limb
Intensely pain
From seconds to
maximum 10 minutes
Calf or foot, seldom
Persisting pain
Sleep disruption
Irritating, burning,
crawling sensations
In episodes
An urge to move
Reduction of symptoms
by activity
No pain ✓✓
Repeating and jerking
Duration 20-30 seconds
Reduced strength of dorsiflexion of ankle, foot and toes was also found in one
study and can be associated with NLC [23]
The response rate of the geriatric clinicians in the focus group of the Delphi
study was 52%, all with > 50% consensus. See Table 5T5
Table 5 Delphi study items
Delphi Study Items Always Mostly Sometimes Never Not known
Are you known with NLC 30* 40 20 0 10**
NLC has a sudden onset 33 56 11 0 0
NLC is only present at night 11 68 11 0 11
Pain and / or intense pain is the main characteristic 10 80 0 0 10
NLC duration varies from seconds to 10 minutes 10 80 0 0 10
NLC location is thigh, calf or foot 33 45 11 0 11
After reduction of NLC there will be pain afterwards 0 50 40 0 10
NLC might be associated with sleep disruption 10 50 20 0 20
NLC is associated with medication use / comorbidity 0 11 67 0 22
NLC might be associated with distress 10 10 60 10 10
Seven criteria differentiating NLC from RLS and PLMD. *Percentages; ** if noexcluded from these survey (n=3)
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of the disorder are. Therefore, we suggest that these de-
velopments indicate extending the scope of clinical care.
The framework introduced in this review provides a nat-
ural guide to future research within the population of
older adults with musculoskeletal disorders during rest
or sleep. Further research on the reliability and valid-
ation of the proposed theoretical framework is necessary
for clinical application and diagnostic accuracy.
In addition, two clinical test procedures were re-
ported for diagnostic application: the forceful knee
flexion test indicated findings of cramps; the examiner
applies a force to overcome knee flexion when testing
in a prone position. Most patients with lumbar disc
herniation comorbid with leg cramps also showed
positive findings during this test, and cramps could
be induced (n= 2) [26, 30]. There is a need for diag-
nostic studies in regard to these clinical tests on NLC
and it will be interesting to assess their benefits as
well [26, 30].
A potential limitation of this review is the lack of pri-
mary studies with the focus on diagnosing NLC in older
adults. Therefore, as much as possible, the risk of bias
was limited by using clearly defined inclusion criteria
and conducting a thorough screening and reviewing
process of the presented literature. Inherent in this
process was the inclusion of patients with several co-
morbidities in the separate studies. Although these co-
morbidities might have influenced the interpretation of
NLC, it does reflect the clinical relevance of patients
with this disorder.
An extensive history taking including the above seven
characteristics may rule out other disorders in diagnos-
ing idiopathic NLC. In conclusion, seven relevant clinical
characteristics have been identified to diagnose patients
with NLC, and specifically differentiate this disorder
from RLS and PLMD. These characteristics enhance the
recognition and diagnosis of this highly prevalent, mus-
culoskeletal sleep-related disorder.
NLC: Nocturnal leg cramps; PLMD: Periodic limb movement disorder; RLS: Restless
leg syndrome
The content is solely the responsibility of the authors, who have all made
substantial contributions to the studys conception and design, the analysis
and interpretation of the data, the draft and revision of the article and the final
approval of the version to be submitted. Mrs A. Hartman of the University
library optimized the search strategy. Also thanks to Mrs A. White and Mr D.
White who edited the manuscript and improved English expression.
This project did not receive any funding.
Availability of data and materials
The full list of extracted abstracts with reasons for exclusion may be obtained
from the corresponding author.
JMH conceived and coordinated the review, participated in search design
and analysis, and drafted the manuscript. JMH designed the search strategy
in collaboration of the library of Hanze University and reviewed the
manuscript. MHG, WP and CvdS contributed to the writing and review of the
manuscript. All authors read and approved the final manuscript.
Competing interests
The authors, JMH, MHG, WP and CvdS, declare that they have no competing
Consent for publication
Not applicable.
Ethics approval and consent to participate
This study has reviewed research materials already published in the public
domain, and with no contact with human subjects; therefore it was exempt
from review by Hanze University Groningen.
Author details
Research Group Healthy Ageing, Allied Health Care and Nursing, Hanze
University of Applied Sciences, Groningen, The Netherlands.
University Campus, Institute for Master Education in Musculoskeletal
Therapies, Amersfoort, The Netherlands.
University of Groningen, University
Medical Centre Groningen, Groningen, The Netherlands.
Received: 19 September 2016 Accepted: 9 February 2017
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... Middle-aged adults aged between 36-55 years who had nocturnal leg cramps, defined as sudden, involuntary and painful knotting sensations in the lower limbs, from last three months and were able to speak and understand English were included in the study whereas, participants diagnosed with any medical conditions (cardiovascular diseases, neurologic deficit, end-stage renal disease, osteoarthritis, peripheral neuropathy, venous insufficiency, peripheral vascular disease), pregnant females, who were unable to understand English or participants who had a history of cancer treatment were excluded from the study. Self-structured questionnaire along with diagnostic criteria from a previous systematic review study consisting of eight questions was used to find out the demographics and frequency of symptoms in patients having nocturnal leg cramps respectively (11). Furthermore, global physical activity questionnaire (GPAQ), perceived stress scale (PSS) and Pittsburgh sleep quality index were used to assess physical activity, stress levels and sleep quality of the participants. ...
... While cramps in hamstrings/thigh and distress were not frequently experienced in NLC episode by participants. Our findings were supported by a systematic review in which distress and hamstrings cramps were seldomly experienced by NLC patients, whereas intense leg pain/cramps in the calf lasting from several seconds to minutes and sleep disruption were experienced by majority of the NLC population (11). Furthermore, association of moderate to severe nocturnal leg cramps with sleep disruption have also been reported in the literature (5). ...
Full-text available
Objective:Nocturnal leg cramps are painful, sleep related involuntary muscle contractions of the lower limb. The objective was to determine the frequency of nocturnal leg cramp symptoms and to compare stress, sleep disturbances, and physical activity between males and females in middle-aged adults having nocturnal leg cramps.Materials and Methods:An analytical cross-sectional survey was conducted on 220 participants in twin cities of Pakistan. Patients between the ages of 35-55 years who experienced nocturnal leg cramps in the previous three months were included, those with any comorbidities were excluded from the study. A diagnostic criterion from a previous systematic review was used to determine and find the frequency of nocturnal leg crampsymptoms. The perceived stress scale, Pittsburgh sleep quality index, and global physical activity questionnaire were used to analyze stress, sleep, and physical activity, respectively.Results:The mean age of all participants was 44.01±6.74 years. The most reported symptom by participants was pain duration lasting from seconds to 10 minutes 219 (99.55%), whereas pain/cramps in thigh/hamstrings 162 (73.64%) was least reported symptom. The mean age of participants in the male and female groups was 44.27±7.65 years, 44.72±6.56 years. Group comparison of gender showed a significant difference with stress (p0.05).Conclusion:The study concludes that majority of the participants experienced all symptoms of the nocturnal leg cramps, whereas leg cramps were the most frequent symptom. Furthermore, females suffering from nocturnal leg cramp reported higher levels of stress compared with males.
... In this survey, leg cramps were defined as "spasmodic, painful, involuntary muscle contractions when resting, lasting from a few seconds to minutes, usually affecting the calf and foot, ie, 'Charley horse.'" 7,8 Because approximately 20% of cases sometimes experience leg cramps during daytime hours, the study authors did not restrict the definition to nighttime leg cramps. ...
This study addresses the prevalence and characteristics of leg cramps in 294 primary care patients (mean age = 46.5 years), with 51.7% reporting leg cramps. Patients who experience resting or exercise-induced leg cramps were more likely to be older and female. Cramp severity averaged 5.6 on a scale of 1-10 and disturbed sleep "sometimes" or "often" in 55% of patients. Most patients did not discuss cramps with their clinician. Our study reveals a possible shift in patients who experience leg cramps to younger age and chronicity. Resting leg cramps should be reviewed by clinicians as a symptom of declining health and advancing aging.
... Aliado a isso, os medicamentos, além das comorbidades, podem ser a causa das cãibras, entre eles é possível citar os diuréticos, estatinas, tiazídicos, beta-agonistas, inibidores da acetilcolinesterase, cimetidina, morfina, esteroides, penicilamina, cardiotrópicos, medicamentos psicotrópicos, antirretrovirais, medicamentos psicotrópicos e além de alguns imunossupressores. (KATZBERG et al., 2019) Vale ressaltar que tanto a sedentarismo como o exercício físico extenuante é tido como causa das cãibras (HALLEGRAEFF et al., 2017). Portanto, isto posto é possível perceber que esse estresse musculoesquelético apresenta etiologias multifatoriais, mas ainda falta consenso em relação a algumas causas. ...
Este livro é uma coletânea de 32 capítulos que abrangem diversos temas na área de saúde. Os capítulos abordam desde doenças comuns como o sangramento uterino anormal e a obesidade infantil, até temas mais específicos, como o uso da toxina botulínica para tratar espasticidade em pacientes pós-AVE e a acupuntura no tratamento da fibromialgia. Além disso, há capítulos que discutem a relação entre hábitos e estilo de vida, como o uso de cigarro eletrônico e exercício físico, com problemas de saúde como doenças cardiovasculares e doenças pulmonares. Também são explorados tópicos como a inteligência artificial na medicina, transtornos psicológicos como o transtorno bipolar e transtornos de personalidade, além de questões sociais como a violência obstétrica e a importância da educação em saúde.
... Patients were asked to complete a questionnaire about their socio-demographic characteristics, their estimated health status (coded as excellent, very good, good, moderate or poor), their weight in kg and height in cm, the number of medical visits in the previous six months, the number of drugs that they were taking per day and the number of NLC in the previous week. We used the following definition of a cramp: 'any sudden, painful and involuntary sensation associated with muscular hardness, occurring in the legs or feet, during sleep or at rest' (3,4,21). Those who had not experienced cramps in the previous week were also eligible to participate in the study. ...
Background: Although nocturnal leg cramps are common, little research is available about their impact on quality of life. This mixed-methods study explored the impact of nocturnal leg cramps on health-related quality of life (HRQoL). Methods: The study included primary care patients (>50 years) who reported suffering from nocturnal leg cramps (2016-2017). In the quantitative phase, patients completed a questionnaire about their HRQoL (SF-36) and the frequency of their cramps, and we computed the SF-36 scores. Then, we conducted a qualitative study using semi-structured interviews with patients with various levels of HRQol to explore their perception of the impact of cramps on their lives. Results: A total of 114 patients (49%) agreed to participate in the quantitative study (mean age: 71, women: 62%) and 15 patients were included in the qualitative study (mean age: 69, women: 67%). The number of cramps in the previous week was low (mean: 1.6 (SD 1.5)). The SF-36 mean physical and mental summary scores were 43 and 50, respectively, and the domain scores were similar to a comparative general population. Whilst some patients reported little interference with their daily lives, others reported a major decrease in their HRQoL. SF-36 scores were not sufficient to describe the cramp-related impairment, as patients from all levels of SF-36 scores reported major impacts of NLC in the interviews. Conclusions: Some patients describe a specific impact of cramps on their lives, regardless of their HRQoL. These patients should be the target of future intervention trials.
Full-text available
Background and Objectives: Muscle cramps are often observed in patients with liver diseases, especially advanced liver fibrosis. The exact prevalence of muscle cramps in outpatients with liver diseases in Japan is unknown. Patients and Methods: This study examined the prevalence of, and therapies for, muscle cramps in outpatients with liver diseases in Tokyo, Japan. A total of 238 outpatients with liver diseases were retrospectively examined. We investigated whether they had muscle cramps using a visual analog scale (VAS) (from 0, none, to 10, strongest), and also investigated their therapies. Results: Muscle cramps were observed in 34 outpatients with liver diseases (14.3%); their mean VAS score was 5.53. A multivariate analysis demonstrated that older age (equal to or older than 66 years) was the only significant factor as-sociated with muscle cramps. The prevalence of muscle cramps among patients with liver diseases seemed not to be higher. The problem was that only 11 (32.4%) of 34 outpatients received therapy for their muscle cramps. Conclusions: Only age is related to muscle cramps, which is rather weak, and it is possible that this common symptom may not be limited to liver disease patients.
Muscle cramps are painful, sudden, involuntary muscle contractions that are generally self-limiting. They are often part of the spectrum of normal human physiology and can be associated with a wide range of acquired and inherited causes. Cramps are only infrequently due to progressive systemic or neuromuscular diseases. Contractures can mimic cramps and are defined as shortenings of the muscle resulting in an inability of the muscle to relax normally, and are generally myogenic. General practitioners and neurologists frequently encounter patients with muscle cramps but more rarely those with contractures. The main questions for clinicians are: (1) Is this a muscle cramp, a contracture or a mimic? (2) Are the cramps exercise induced, idiopathic or symptomatic? (3) What is/are the presumed cause(s) of symptomatic muscle cramps or contractures? (4) What should be the diagnostic approach? and (5) How should we advise and treat patients with muscle cramps or contractures? We consider these questions and present a practical approach to muscle cramps and contractures, including their causes, pathophysiology and treatment options.
Only a few studies report the socioeconomic and health-related quality of life (QoL) impacts of sleep-related movement disorders (SRMDs) such as restless legs syndrome (RLS), sleep bruxism (SB), sleep-related rhythmic movement disorder (RMD), and sleep-related leg cramps (SLC). Often, a patient's partner or parent are first to notice the symptoms of an SRMD and requests a medical evaluation. The socioeconomic impact of SRMDs can be measured: (1) directly through the financial costs of healthcare for treatment; (2) estimated indirectly by the effects on an individual's quality of life (QoL); and (3) the effects on society by loss of work productivity.
Full-text available
Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
Full-text available
IntroductionPatients with lumbar spine disease sometimes complain of nocturnal leg cramps. We sought to investigate the effectiveness of blocking the medial branch of the deep peroneal nerve as treatment for nocturnal leg cramps after spinal surgery for lumbar spine disease.Methods We evaluated 66 postoperative patients in this prospective comparative study of a group of patients with a nerve block (n = 41) and a control group without (n = 25). In the block group, the medial branch of the deep peroneal nerve was blocked at the distal two-thirds of the interspace between the first and second metatarsals using 5.0 mL of 1.0% lidocaine.ResultsTwo weeks after the block, the frequency of nocturnal leg cramps was reduced to less than a quarter of pretreatment baseline frequency in 61.0% of patients (n = 25) and less than half in 80.5% (n = 33). In the control group, the frequency of the leg cramps was reduced from baseline in 32.0% of patients (n = 8), and was unchanged or increased in 68.0% (n = 17) at 2 weeks. Cramp frequency was reduced to less than a quarter or less than half of baseline frequency in a significantly (P < 0.05 and P < 0.01, respectively) larger percentage of patients in the block group. The severity of each cramp was less in about two-thirds of patients (63.4%; n = 26) in the block group and was unchanged in one-third (31.7%; n = 13).Conclusions Blocking the medial branch of the peroneal nerve can be an effective, long-lasting, and simple treatment with low risk for nocturnal cramps sustained after lumbar spine surgery.
Full-text available
It has been anecdotally reported that nocturnal leg cramps in pregnant women are worse in summer. We analyzed population-level data to determine whether the symptom burden of nocturnal leg cramps is seasonal in the general population. We examined time-series data for 2 independent measures of the symptom burden of leg cramps: (a) new quinine prescriptions (reflecting new or escalating treatment of leg cramps) from December 2001 to October 2007 among adults aged 50 years and older, which were obtained from linked health care databases that contain the prescribing information for the 4.2 million residents of British Columbia, Canada; and (b) the Internet search volume from February 2004 to March 2012 for the term "leg cramps" (reflecting public interest), which we obtained from Google Trends data and geographically limited to the United States and Australia. We assessed seasonality by determining how well a least-squares sinusoidal model predicted variability in the outcomes. New quinine prescriptions and Internet searches related to leg cramps were both seasonal, with highs in mid-summer and lows in mid-winter, and a peak-to-peak variability that was about two-thirds of the mean. Seasonality accounted for 88% of the observed monthly variability in new quinine prescriptions (p < 0.001) and 70% of the observed variability in Internet searches related to leg cramps (p < 0.001). New quinine prescriptions and Internet searches related to leg cramps were seasonal and roughly doubled between the winter lows and summer highs. Why a disorder of peripheral motor neurons displays such strong seasonality warrants exploration. © 8872147 Canada Inc.
Full-text available
Study design: Prospective cohort study with questionnaire. Purpose: To compare the treatment outcome of nocturnal leg cramps in lumbar spinal canal stenosis (LSCS) patients on conservative treatment with historical surgical cohorts and to determine the sensitivity and specificity as well as positive predictive value and negative predictive value of knee flexion test suggested for LSCS patient. Overview of literature: True prevalence of nocturnal leg cramps in LSCS patients as well as the clinical outcome of its surgical treatment have been reported. Methods: A questionnaire suggested from previous study with minor modifications was used in this study. Clinical data was collected. Knee flexion test was performed in two groups. Results: The prevalence of nocturnal leg cramp was higher in the LSCS group compared to the control group (second group). In LSCS patients, 38 (88%) had improved leg cramps after the conservative treatment, 3 (6.97%) remained unchanged, and 2 (4.6%) had worsened leg cramps. Of the 43 patients, 21 (48.8%) had no disturbance to their activities of daily living. In the LSCS group, the sensitivity and specificity of the knee flexion test was 53.5% and 33.3%, respectively. The knee flexion test in the LSCS group had a positive predictive value and a negative predictive value of 65.71% and 23.1%, respectively. Conclusions: Our study demonstrated that nocturnal leg cramps were significantly more frequent in LSCS patients than in the control group.
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Appraisal Correspondence Prophylactic stretching is unlikely to prevent nocturnal leg cramps In order to reduce the frequency of nocturnal leg cramps, leg stretching before sleep is commonly recommended. A little over a year ago in this journal, Hallegraeff et al 1 authored the first randomised controlled trial to support this practice – demonstrating 1.2 fewer cramps per night and less-severe cramp pain in the stretching group, compared to those receiving no treatment. Missing from the analysis of this trial, however, was an explanation of why (despite similar recruitment methods and similar inclu-sion/exclusion criteria) the cramp rate in the control group differed so dramatically from what had been observed in other randomised trials. Cochrane systematic reviews of both quinine (13 trials with 952 subjects) and magnesium (4 trials with 213 subjects) for the prophylaxis of rest cramps show mean cramp rates in placebo controls of 4.4 and 4.35 cramps/week. 2,3 In contrast, the control group cramp rate in the trial by Hallegraeff et al was 16.
From the ancients to the present day, the importance of sleep has seldom been disputed, but it has never had top billing in comparison to other components of healthy living. Now, however, it seems that the combined critical mass of research, the needs of the population, and the shifting weight of professional interest is pushing sleep to the academic and research forefront. The Oxford Handbook of Sleep and Sleep Disorders provides a review of knowledge about current research and clinical developments in normal and abnormal sleep. The book comprises three sections: Section I covers the basics of normal sleep, its functions, and its relationships to emotions, cognitions, performance, psychopathology, and public health and safety issues. Section II addresses abnormal sleep, including disorders like insomnia, parasomnias, circadian rhythm disorders, and sleep apnea. An informed classification of sleep/wake disorders is presented along with a protocol for assessing sleep-wake complaints and evidence-based treatment options. Section III provides a developmental perspective on sleep and sleep problems in childhood, adolescence, and in late life, and a discussion of sleep disturbances in selected special populations.
The aim of the study was to define the features, prevalence, and pathophysiology of therapy for muscle cramps in cirrhotic patients. The first protocol study included 294 cirrhotic patients and 194 age- and sex-matched controls. Controls were defined as inpatients or outpatients without any clinical and laboratory evidence of liver disease. Features and prevalence of muscle cramps were defined on the basis of a standard questionnaire. As far as the pathophysiological associations of muscle cramps were concerned, the following parameters were evaluated: mean arterial pressure (MAP), nutritional status, liver function tests, plasma volume (PV), plasma renin activity (PRA), and electrolyte, mineral, and acid-base status. The prevalence of cramps was higher in cirrhotic patients than in controls, and it was related to the duration of recognized cirrhosis and to the severity of liver function impairment. At a multiple regression analysis, the presence of ascites, low values of MAP, and high values of PRA were the independent predictive factors for the occurrence of cramps in cirrhosis. In the second protocol study, the effects of a sustained expansion of the effective circulating volume induced by intravenous infusion of human albumin were compared with those of a placebo in 12 cirrhotic patients with more than three cramp crises a week. Compared with the placebo, albumin reduced the cramp frequency (P < .01). In conclusion, an increased prevalence of true muscle cramps occurs in patients with cirrhosis. Our data indicate that the pathophysiological link between cirrhosis and cramps may be represented by the reduction of the effective circulating volume. They also indicate that weekly infusion of human albumin may be an effective treatment for cramps in cirrhosis. (Hepatology 1996 Feb;23(2):264-73)