Neurology International 2019; volume 11:8198

Dropped head syndrome due inflammatory polyneuropathy (CIDP),11 to neuromuscular disorders: neuromuscular causes include myasthenia Correspondence: Ahmet Z. Burakgazi, gravis (MG),12-14 Lambert-Eaton myasthe- Neuroscience Section, Department of Clinical manifestation and nia syndrome (LEMS),15 muscular causes Medicine, Virginia Tech Carilion School of evaluation includes primary inflammatory such as Medicine, 3 Riverside Circle, Roanoke, VA ,16 scleromyositis,17,18 isolated 24016, USA. inflammatory axial ,19 primary Tel.: +1.540-521-4592. Ahmet Z. Burakgazi, Perry K. E-mail: [email protected] Richardson, Mohammad Abu-Rub non-inflammatory such as nemaline myopa- 20-22 thy, mitochondrial myopathy, congeni- Key words: Dropped head syndrome, neuro- Virginia Tech Carilion School of 23 24 tal myopathy, FSHD, and isolated neck muscular disease. Medicine, Roanoke, VA, USA extensor myopathy (INEM).19 Contributions: the authors contributed equally.

Conflict of interest: the authors declare no Abstract General approach: clinical mani- potential conflict of interest. festation and evaluation In this article, we discuss the clinical Funding: none. approach to patients with dropped head syn- DHS occurs as a result of of drome and identify the various neuromus- posterior neck muscles. It usually disap- Received for publication: 11 June 2019. cular causes of dropped head syndrome pears with supine position. The common Accepted for publication: 18 June 2019. including muscle, neuromuscular junction, chief complaints are “chin on the chest” and This work is licensed under a Creative peripheral nerve and motor neuron etiolo- “difficulty maintaining a forward gaze”. It gies. We aim to increase awareness of Commons Attribution NonCommercial 4.0 may contribute to and has cos- License (CC BY-NC 4.0). recognition the entity of dropped head syn- metic and social implications.1,12,19,25 drome and factors that may predict response Semispinalis cervicis and semispinalis capi- ©Copyright: the Author(s), 2019 to immunomodulating therapy in dropped tis are primarily responsible for neck exten- Licenseeonly PAGEPress, Italy head syndrome. sion. DHS is thought to be directly related Neurology International 2019; 11:8198 to weakness or laxity of the semispinalis doi:10.4081/ni.2019.8198 cervicis muscles.1,25 During the evaluation of dropped head,use Introduction providers first should rule out structural dis- tive weakness pattern (as in IBM), and The dropped head syndrome (DHS), eases of the cervical spine. To differentiate pelvic girdle weakness (as in most general- also known as the floppy head syndrome, NM causes from non-NM causes is very ized ) should be assesses care- was first described as in 1986.1 It was ini- important. In NM causes, a significant fully.1,2,25,27 tially recognized in 12 patients with neuro- weakness of neck extensors is usually Following physical examination, a muscular (NM) disorders. This syndrome is observed. In non-NM causes, imbalance of provider should decide if further imaging defined by weakness of neck extensor mus- neck muscle tone leads to dystonic antero- tests are warranted. X-rays can be ordered cles against gravity with or without weak- collis. It is paramount important to identify to rule out kyphosis, fractures, and arthritis. 1,2,12,19,25 ness of neck flexor muscles. It can be an potential treatable causes. Magnetic resonance imaging (MRI) is supe- isolated clinic entity presenting with diffi- A deliberate and detailed history taking rior to Computed tomography (CT) to culty raising the head or it can be part of the is a key factor for an accurate diagnosis and imagine soft tissue includes tendons, liga- generalized muscular disease manifestation. important clues can be gathered from the ments, fascia, fibrous tissues, fat, synovial In the first report, definite diagnosis was history. Firstly, a provider should identify membranes, muscles, and nerves.28,29 established in 9 patients; pattern of involvement and characteristics Contrast enhancement is sensitive to detect in 4; motor neuron disease in 3; polymyosi- of weakness. These questions should be inflammation. MRI imaging demonstrates tis (PM), sclerodermatomyositis Non-commercial (SDM), asked if a patient has isolated neck extensor fatty infiltration, edema, and/or atrophy of and facioscapulohumeral dystrophy weakness or diffuse weakness; if a patient the neck musculature.28 Radiological imag- (FSHD) in 1.1 Then in 1992, Suarez and has fatigable weakness or diurnal variation; ing particularly MRI is useful for determin- Kelly described a non-inflammatory if there is any cranial and/or bulbar muscle ing biopsy sites in selective cases.28,29 myopathy affecting predominantly neck involvement; if there is any respiratory Electrodiagnostic (EDx) studies pro- extensors in four patients, aged 63 to 81 ; and if there are any asso- vide valuable information in the diagno- years and they named the DHS as a new ciated symptoms such as autonomic symp- sis.30,31 The needle study should include clinical disorder, characterized by severe toms. Detailed family and developmental cervical and thoracic paraspinal, sternoclei- weakness of neck extensors with milder history should be taken as well as history of domastoid muscle, and trapezius muscles. weakness of shoulder girdle and proximal onabotulinumtoxin A injections.1,2,16,19,25,26 Facial and tongue muscles should be tested arm muscles. After detailed history, cautious and if any weakness is detected. DHS is relatively rare condition that complete physical examination should be Electromyographer should be careful not to may occur as a result of several neurologi- performed to collect more clues for an accu- overestimate paraspinal muscles finding cal, neuromuscular, muscular, and other rate diagnosis. In the physical exam, upper during the needle testing since normal causes. Neurological causes includes amy- and/or lower motor signs, muscle paraspinal motor unit action potentials have otrophic lateral sclerosis (ALS),2,3, wasting/atrophy (as in motor neuron dis- smaller amplitudes and a shorter duration, Parkinson disease4, multiple system atro- ease) , skin findings (as in dermatomyosi- but the recruitment is normal as opposed to phy,4,5 cervical dystonia,6 postpolio syn- tis), ocular and bulbar weakness (as in MG), reduced or early recruitment.30-32 drome,7 cervical myelopathy,8-10 chronic facial weakness (as in FSHD), highly selec- Muscle biopsy can be considered in

[page 52] [Neurology International 2019; 11:8198] Review selected cases. Most of the biopsies are Another retrospective study,3 including The pathogenesis of DHS in ALS may taken from shoulder girdle muscles includ- 683 patients with ALS from India showed 9 be preferential involvement of paraspinal ing deltoid and trapezius muscles.30,33 of the patients (1.3%) had severe weakness anterior horn cells. Electromyography Biopsy from cervical paraspinal muscles of neck extensor muscles observed as an (EMG) test shows denervation with no are more valuable, but more challenging early feature, or developing during the later myopathic features. Muscle biopsy is usual- because small and larger muscles are inter- stages of the disease. The mean of affected ly consistent with neurogenic atrophy.2,12 mingled and it is difficult to know exactly patients was 53.3 (±10.3) (range 33 to 65). DHS may cause neck pain and discom- which muscles should be biopsied.30,32 Six of them developed head drop as an early fort in ALS patients. DHS can cause severe Muscle biopsy may provide valuable infor- feature (mean interval from onset of illness impairments in activities of daily living mation particularly in diagnosis of inflam- was 11.6 months) and three has late onset (ADL) such as eating, dressing so ALS matory muscle diseases such as size vari- (between three and eight years after onset).3 patients with DHS are more dependent in ability with fibrosis (Figure 1) and inflam- In their series, none of patients developed ADL.12,34 We advise ALS patients with mation with some necrotic fibers (Figure 2). respiratory difficulties but all had swallow- DHS to wear a neck collar, which improve Ultrasound guided biopsy may be helpful, ing difficulties and social embracement.3 their posture, swallowing, and neck pain. but not is not widely used.

DHS in amyotrophic lateral sclerosis Dropped head is a rare manifestation of ALS occurring around 1-3% of patients.34 Dropped head is usually an early feature of ALS but it is usually not the presenting symptom. Neck flexor muscles weakness is only usually worse than neck extensor muscles in ALS patients. DHS in ALS patients has been reported in few case reports.2,3,34 A single-hospital-based retrospective study34 use from Japan including 105 sporadic ALS patients showed the incidence rate of DHS was 2.9% (3/105). The ages were 56, 63, and 53 years. The initial symptoms of the patients were bulbar palsy in two patients and weakness of the upper limb in one patient.34 The onset to DHS was 14, 4 and 26 months after the onset of illness. Patients with prominent legs weakness did not Figure 1. The picture demonstrates size variability with fibrosis. develop DHS in their study.34

Non-commercial

Figure 2. The pictures demonstrate inflammation with some necrotic fibers.

[Neurology International 2019; 11:8198] [page 53] Review

and mycophenolate mofetil. Only one had DHS in neuromuscular junction full remission and two showed some DHS in peripheral neuropathy disorders improvements. The pathological relationship between Chronic inflammatory demyelinat- Myasthenia gravis MG and axial myopathy is unclear. Most of ing polyneuropathy Drooped head is a well-recognized fea- the reported cases are in their late 70s or DHS is very rare presentation of CIDP. ture of MG even in the absence of ocular or early 80s. Mechanical stretch injury, loss of Two cases have been reported on DHS with bulbar signs. It can be associated with or tissue elasticity with aging, chronic use of CIDP. In the first case report, a 19-year-old contribute to respiratory muscle weakness. steroids/immunosuppressive agents may female with history of Guillain-Barre syn- Dropped head can be the presenting sign of contribute myopathy process.36-38 EMG test drome with fair recovery developed marked only sign of MG. One retrospective study,35 can be helpful for differential diagnosis but weakness of the neck extensors that she was including 146 patients with generalized MG should be performed by experienced elec- unable to light her head. The detailed showed 15 patients (10%) of the patients tromyographer to avoid under or overesti- worked-up including EDx testing, cerebral developed head drop. Of these 15 patients, mate. Cervical MRI imaging is useful to spinal fluid (CSF) analyses were consistent acetylcholine receptor binding detect atrophy of cervical paraspinal and with CIDP. She was treated with (AchR Ab) were positive in 14, and anti- surroundings muscles.36-38 plasmapheresis, prednisone, and MuSK antibodies positive in 1.35 Dropped In our opinion, cervical paraspinal but she did not have any head symptoms in MG patients with posi- muscle biopsy and cervical imaging are not remarkable improvement in neck extensors tive AchR Ab improved with treatments, but required as a part of the initial work up in and shoulder girdle muscles. She had to use 11 the patient with positive anti-MuSK Ab was myasthenia patients with head drop since it cervical collar for neck stabilization. The 40 refractory to multi treatments including will not change treatment approaches. second report was reported in 2006, a 63 prednisone, plasmapheresis, and mycophe- Cervical paraspinal muscle biopsy and cer- year-old patient presented with slowly pro- nolate mofetil. Shortcoming of the study vical imaging should be considered in treat- gressive weakness of the neck extensor was no imaging, EMG or muscle biopsies ment-refractory cases. muscles developing a dropped head syn- findings were reported.35 dromeonly over a 12 months period. The Another case series study reported 13 Lambert-Eaton myasthenic detailed investigation including EMG, MRI, CSF analysis were inconclusive. MG cases with dropped head. Of those syndrome Within two years, she developed fascicula- patients, 8 were positive with AchR Ab; 3 LEMS is an autoimmune disease affect- tions, atrophic paresis of the limbs and res- were positive with MuSK Ab; and 2 were ing neuromuscular junction due to antibod- usepiratory muscle involvement with consecu- sero negative. Eight of the patients had cer- ies production against voltage gated calci- tive respiratory failure. The postmortem vical imaging and one showed atrophic um channels (VGCC). DHS is very rare neuropathological assessment demonstrated muscle changes. Two of them underwent clinical presentation of LEMS. LEMS syn- CIDP with involvement of the autonomic thymectomy. Six patients had full remis- drome presenting with DHS has been ganglia and the intramural plexus. Due to sion, and seven has significant improve- reported twice. The first case was associat- the complexity of the case the clinical diag- ment with therapy. The outcome is usually ed with antibodies against P/Q VGCC and nosis of a CIDP as cause of the dropped good with effective control of myasthenic his symptoms and electrophysiological head syndrome was able to make after the symptoms. Paraspinal muscles biopsies abnormalities improved with oral pred- postmortem pathological examination.40 were not performed in the study. nisone following plasmapheresis.15 The Treatment-refractory MG cases should second case was associated with autoanti- Charcot Marie tooth disease type 4C be reassessed for possible concomitant axial bodies against N-type VGCC.39 The patient In another interesting report, an 11- myopathy. First case was reported by presented with symmetric paresis (3/5) of year-old boy presented with proximal mus- Rodolico in 2014.36 The patient presented the head extensors with pronounced muscle cle weakness with facial involvement as with ocular, bulbar, and shoulder girdle atrophy. She had more pronounced weak- well as dropped head and severe scoliosis. weakness preceded head drop. The initial ness in the evening. She had partial but sud- The detailed work up showed sensorimotor blood work up showed normal CK, positive den restoration of weakness with intra- demyelinating polyneuropathy and genetic AchR binding antibodies. Cervical MRI venous edrophonium. The initial blood test Non-commercial test confirming Charcot Marie Tooth dis- showed atrophy and fatty replacement of was negative for myasthenia gravis antibod- ease type 4C.41 Therefore early-onset inher- neck extensor muscle. EMG test showed ies. She was initially admitted for sero-neg- ited polyneuropathies should also be includ- sporadic fibrillation and myopathic motor ative MG and treated with pyridostigmine ed in the differential diagnosis of patients unit action potentials (MUAPs) limited to and methyl-prednisolone. She was dis- with proximal muscle wasting associated paraspinal muscles. Deltoid muscle biopsy charged home in an improved state. She with dropped head syndrome.41 showed scattered centralized nuclei. The was readmitted after 4 weeks with worsen- case was refractory to pyridostigmine ing of neck weakness and a progressive and/or prednisone.36 Eight more cases with general muscle weakness as well as 39 MG and concomitant axial myopathy have dysarthria and dysphagia. The further DHS in muscle disorders been reported since then. Seven with posi- work up showed positive N-type VGCC tive AchR Ab and positive MuSK Ab. All and was treated with unmodified medica- The DHS occurs in a variety of muscu- patients’ EMG showed myopathic MUAPs tion with continuous and significant lar disorders including primary inflammato- in paraspinal muscles. Three had biopsies improvement. The serum titer of N-type ry such as PM,16,42 scleromyositis showing fiber atrophy, endomysial inflam- VCGG specific antibodies dropped to nor- (SM),17,18 isolated inflammatory axial mation with fibrosis. Five were refractory to mal that correlated with clinical improve- myopathy19, primary non-inflammatory multi-therapy including thymectomy, pyri- ments.39 , mitochondrial myopa- dostigmine, prednisone, intravenous thy,20-22 ,23 FSHD,24 immunoglobulins (IVIG), plasmapheresis, and isolated neck extensor myopathy.19

[page 54] [Neurology International 2019; 11:8198] Review

Wide spectrum pathological processes asso- standing positions. The detailed investiga- ciated with the myopathic DHS ranging Isolated neck extensor myopathy tion ended up with a diagnosis of anti-glu- from non-inflammatory muscle necrosis to INEM was first described in four tamic acid decarboxylase-associated a classic inflammatory . patients in 1996.19 The author reported four inflammatory myopathy. Her symptom cases presented with neck extensor weak- improved after intravenous immunoglobu- Polymyositis/Scleromyositis ness. The age ranged from 65 to 85 years lins (0.4 g/kg/day for 5 days) followed by Inflammatory myopathies can cause old. Only one patient had mild flexion, and prednisone 25 mg/day for 2 months.48 DHS. In one report, two patients with myo- shoulder abduction weakness. EMG pathic dropped head syndrome presented showed myopathic findings in cervicotho- Adult-onset nemaline myopathy with a predominant weakness of the neck racic paraspinal muscles. Results of cervical Another cause of dropped head is adult- extensor muscles. One patient had a good paraspinal muscle biopsies demonstrated onset nemaline myopathy.49 In one case,49 response to steroid and a histopathological nonspecific myopathic features. The reported in 1999, a 59-year-old Greek assessment revealed PM.16 The other one detailed neurological investigations were painter complained of progressive pain and did not have a good response to steroid but inconclusive.19 Treatment trials with pyri- weakness in neck extensors, proximal legs, the weakness was stabilized after initial dostigmine bromide and prednisone were and shoulders for 1 year. Cramps, twitching, progression. The muscle biopsy was consis- attempted in 3 of them with no clinical and atrophy were detected in the affected tent with a necrotizing myopathy with no improvement. All patients had initial pro- muscles. EMG showed myopathic abnor- evidence of inflammation.16 In another gression of weakness, followed by stabiliza- malities in proximal muscles with normal report,42 a 69 year-old male with history of tion of neck weakness with no changes in nerve conduction studies (NCS). Muscle PM presents with DHS due to a relapse of follow up.19 The responsiveness of treat- biopsy demonstrated prominent muscle DM. DHS improved by 60-70% with 2 ment of INEM is debatable. INEM usually fiber atrophy and centrally located nuclei months with methyl-prednisone (80 mg/d) has a poor response to immunosuppressive and electromicroscopy revealed that the that was tapered down to 4 mg within 8 therapy because it is a non-inflammatory atrophic fibers contained large arrays of months.42 myopathy.19 However, recent publications osmiophilic oval structures, composed of Z- Two patients were reported with DHS have challenged this general acceptance.43- bandonly material.49 In the same report, the associated with SM, also known as sclero- 45 Muppidi et al.43 reviewed four patients authors reviewed previously published 11 17 derma-PM . One of the with INEM who received one or more well-documented cases of adult-onset cases,53 year-old women, presented with immunosuppressive agents and showed nemaline myopathy and they showed that 17 DHS with mild dysphagia. She had wast- neck strength improved by one or greateruse on neck weakness was mentioned in seven ing of the neck extensor as well as the the Medical Research Council scale in all cases, and four of them had severe extensor shoulder girdle muscles. Serum creatinine patients with a peak response between 3 and weakness.49 After that report, several cases kinase, lactate dehydrogenase, aspartate and 6 months after treatment initiation. They of nemaline myopathy related DHS are alanine aminotransferase were elevated. recommended a trial of immunosuppressive reported.21,22,50,51 EMG findings showed myopathic process agents to patients with INEM.43 As a defini- with early recruitment in deltoid, iliopsoas, tion, INEM is a non-inflammatory myopa- Amyloidosis and quadriceps muscles. A muscle biopsy of thy but focal myositis could be missed on In another report, a 77-year-old man the left deltoid showed a mild and diffuse muscles biopsy that may explain immuno- with history of lymphoma and neck radia- process of necrosis and regeneration associ- suppressive responsiveness in some INEM tion presented with neck extensor weak- ated with major perivascular inflammatory cases.43,45 ness.52 Needle EMG showed myopathic infiltrate locates in endomysial, perimysial changes, and biopsy of cervical paraspinal and epimysial tissues. The autoantibody Facioscapulohumeral muscular dys- muscle demonstrated amyloid deposition in screen revealed positive antinuclear anti- trophy blood vessels.52 In another similar case, the body (1/640),mildly positive antineu- further investigation revealed DHS with trophilic cytoplasmic (1/40), posi- FSHD is rare reason of DHS. It was reported that a patient with FSHD devel- proximal myopathy caused by AL amyloi- tive rheumatoid factor at 128 UI/l (normal dosis.53 Thus amyloidosis should consider b30), and positive anti PM-Scl antibody. oped dropped head caused by severe wast- Non-commercial46 in the differential diagnosis of DHS. Cervical MRI without gadolinium was ing of neck muscles. In Kazakov et al. 47 unremarkable. She was treated with pred- study, the review of 200 FSHD patients nisone 1mg/kg. The dysphagia resolved showed only 4 patients had slight or moder- ate weakness of neck extensor muscles. In within 2 weeks and motor weakness rapidly Mitochondrial myopathy improved. Within two months, she was able the same series, some patients with severe to keep her head straight. Her condition pro- muscle atrophy and weakness of muscles Mitochondrial myopathy should be part gressively improved for one year, then fixing the scapula demonstrated visible of the differential diagnosis of DHS, partic- remained stable.17 The other case,18 51- dropped head because of abnormal posture ularly when more common causes are 47 year-old man presented with neck pain and of the shoulder girdle. excluded. DHS was the presenting manifes- inability to maintain the head erect. The tation of mitochondrial myopathy in two detailed blood, pathological investigations Anti-glutamic acid decarboxylase- cases.54 Detailed neurological work-up were consistent with scleromyositis. He was associated inflammatory myopathy were performed to rule out common causes. treated with prednisone on a 60 mg/d step- DHS is a complex and perplexing con- The work up revealed elevated serum lac- down dosage with subcutaneous methotrex- dition that has been reported in different tate and mitochondrial proliferation in mus- ate at a dose of 25 mg/wk, which resulted in neurological disease. In one of the interest- cle biopsy.54 In another report, DHS was remarkable improvement in neck weakness ing report,48 a 78-year-old woman present- reported as result of possible multi-organ and limitations within 1 month with nor- ed with a 10-month history of difficulty in mitochondriopathy, manifesting as malized muscle enzymes.18 keeping her head up during sitting and Parkinsonism, tetraspasticity, dilative car-

[Neurology International 2019; 11:8198] [page 55] Review diomyopathy, short stature, osteoporosis, Psychiatry 2003;74:683-6. Alonso S, et al. Dropped head syn- and myopathy. In this case, neurological 4.Askmark H, Eeg-Olofsson K, drome in a patient with scleromyositis. examination showed prominent neck exten- Johansson A, et al. Parkinsonism and J Clin Rheumatol 2013;19:32-4. sor weakness, weakness of the shoulder gri- neck extensor myopathy: a new syn- 19. Katz JS, Wolfe GI, Burns DK, et al. dle, cogwheel rigidity, and tetraspacticity. drome or coincidental findings? Arch Isolated neck extensor myopathy: a The further tests showed elevated serum Neurol 2001;58:232-7. common cause of dropped head syn- lactate, myogenic findings in needle EMG, 5. Diederich NJ, Goebel HH, Dooms G, et drome. Neurology 1996;46:917-21. and myogenic abnormalities with weak al. Camptocormia associated with focal 20. Maruyama T, Hanyu N, Maruyama K, staining of cytochrome oxidase in muscle myositis in multiple-system atrophy. et al. [Clinical and pathological studies biopsy. No improvement of the clinical Mov Disord 2006;21:390-4. on two patients with adult-onset nema- symptoms with anti-Parkinson medications. 6. Mezaki T. [Clinical characteristics and line myopathy]. Rinsho Shinkeigaku Based on those findings, mitochondriopa- treatment of dystonia]. Rinsho 1990;30:738-44. thy with multi-organ involvement was sus- Shinkeigaku 2011;51:465-70. 21. Katirji B, Hachwi R, Al-Shekhlee A, et pected.55 7. Fast A, Thomas MA. The “baseball cap al. Isolated dropped head due to adult- orthosis”: a simple solution for dropped onset nemaline myopathy treated by Other myopathies head syndrome. Am J Phys Med posterior fusion. Neurology DHS can be caused by several different Rehabil 2008;87:71-3. 2005;65:1504-5. types of primary or secondary myopathies. 8. Kawaguchi A, Miyamoto K, Sakaguchi 22. Erro M, Echavarri C, Tunon T. It is difficult to summarize all those reports Y, et al. Dropped head syndrome associ- [Dropped head syndrome secondary to in this article. In this section, we only pro- ated with cervical spondylotic myelopa- nemalinic myopathy]. Neurologia vide the name of myopathies and its related thy. J Spinal Disord Tech 2004;17:531- 2006;21:376-77. references. It is paramount important to rec- 4. 23. Pasqualin LM, Reed UC, Costa TV, et ognize the causes of secondary myopathies 9. Nakanishi K, Taneda M, Sumii T, et al. al. Congenital with that may be a treatable cause of DHS. Other Cervical myelopathy caused by dropped dropped head linked to the LMNA gene reasons of secondary myopathies include head syndrome. Case report and review inonly a Brazilian cohort. Pediatr Neurol Cushing syndrome,56 carnitine deficien- of the literature. J Neurosurg Spine 2014;50:400-6. cy,57-59 hypothyroidism,60-62 hypokalemia,63- 2007;6:165-8. 24. Liewluck T, Milone M, Mauermann 65 hyperparathyroidism,66-68 and post-radia- 10. Rahimizadeh A, Soufiani HF, ML, et al. A novel VCP mutation under- tion neck extensor myopathy.69-72 Rahimizadeh S. Cervical Spondylotic lies scapuloperoneal muscular dystro- Myelopathy Secondary to Droppeduse phy and dropped head syndrome featur- Head Syndrome: Report of a Case and ing lobulated fibers. Muscle Nerve Review of the Literature. Case Rep 2014;50:295-9. Conclusions Orthop 2016;2016:5247102. 25. Martin AR, Reddy R, Fehlings MG. 11. Hoffman D, Gutmann L. The dropped Dropped head syndrome: diagnosis and DHS is relatively rare condition that head syndrome with chronic inflamma- management. Evid Based Spine Care J may occur as a result of several neurologi- tory demyelinating polyneuropathy. 2011;2:41-7. cal, neuromuscular, muscular, and other Muscle Nerve 1994;17:808-10. 26. Hogan KA, Manning EL, Glaser JA. causes. It is important to differentiate NM 12. Petiot P, Vial C, de Saint Victor JF, et al. Progressive cervical kyphosis associat- and non-NM causes to offer best treatment [Dropped head syndrome: diagnostic ed with botulinum toxin injection. options to patients. Detailed history taking, discussion apropos of 3 cases]. Rev South Med J 2006;99:888-91. physical examinations are key to make an Neurol (Paris) 1997;153:251-5. 27. Puruckherr M, Pooyan P, Dube D, et al. accurate diagnosis. EDx studies, MRI imag- 13. D’Amelio M, Di Benedetto N, The dropped head sign: an unusual pre- ing, and paraspinal muscle biopsy can pro- Ragonese P, et al. Dropped head as an senting feature of myasthenia gravis. vide valuable information in selected cases. unusual presenting sign of myasthenia Neuromuscul Disord 2004;14:378-9. We aim to increase awareness of recogni- gravis. Neurol Sci 2007;28:104-6. 28. Gaeta M, Mazziotti S, Toscano A, et al. tion the entity of dropped head syndrome 14. Spengos K, Vassilopoulou S, “Dropped-head” syndrome due to iso- and factors that may predict responseNon-commercial to Papadimas G, et al. Dropped head syn- lated myositis of neck extensor mus- immunomodulating therapy in dropped drome as prominent clinical feature in cles: MRI findings. Skeletal Radiol head syndrome. MuSK-positive Myasthenia Gravis with 2006;35:110-2. thymus hyperplasia. Neuromuscul 29. Hashimoto K, Miyamoto H, Ikeda T, Disord 2008;18:175-7. Akagi M. Radiologic features of References 15. Ueda T, Kanda F, Kobessho H, et al. dropped head syndrome in the overall “Dropped head syndrome” caused by sagittal alignment of the spine. Eur 1. Lange DJ, Fetell M, Lovelace RE, et al. Lambert-Eaton myasthenic syndrome. Spine J 2018;27:467-74. The floppy head syndrome. Ann Neurol Muscle Nerve 2009;40:134-6. 30. Suarez GA, Kelly JJ, Jr. The dropped 1986;20:133. 16. Goh KJ, Wong KT, Tan CT. Myopathic head syndrome. Neurology 2. Jokelainen M. Amyotrophic lateral scle- dropped head syndrome: a syndrome of 1992;42:1625-7. rosis in Finland. II: Clinical characteris- mixed aetiology. J Clin Neurosci 31. Lin HN, Nagaoka M, Hayashi Y, tics. Acta Neurol Scand 1977;56:194- 2000;7:334-6. Yonezawa I. [Pathophysiological analy- 204. 17. Garcin B, Lenglet T, Dubourg O, et al. sis of dropped head syndrome caused 3. Gourie-Devi M, Nalini A, Sandhya S. Dropped head syndrome as a presenting by various diagnoses - based on surface Early or late appearance of “dropped sign of scleromyositis. J Neurol Sci EMG findings and responses to physio- head syndrome” in amyotrophic lateral 2010;292:101-3. therapy]. Rinsho Shinkeigaku sclerosis. J Neurol Neurosurg 18. Fernandez-Serna M, Arboleya L, 2013;53:430-8.

[page 56] [Neurology International 2019; 11:8198] Review

32. Morino K, Kita Y, Yoneda Y, et al. of isolated neck extensor myopathy trum. Am J Phys Med Rehabil [Dropped head plus syndrome; a case responding favorably to immunothera- 2007;86:970-6. report]. Rinsho Shinkeigaku. py. J Clin Neuromuscul Dis 59. Vengalil S, Preethish-Kumar V, 2003;43:556-9. 2013;15:73-6. Polavarapu K, et al. Fatty acid oxidation 33. Oerlemans WG, de Visser M. Dropped 46. Ichikawa Y, Yamada H, Motoyoshi Y, et defects presenting as primary myopathy head syndrome and bent spine syn- al. Abnormal head drooping in and prominent dropped head syndrome. drome: two separate clinical entities or facioscapulohumeral muscular dystro- Neuromuscul Disord 2017;27:986-96. different manifestations of axial myopa- phy. Rinsho Shinkeigaku 1996;36:503- 60. Kendall-Taylor P, Turnbull DM. thy? J Neurol Neurosurg Psychiatry 6. Endocrine myopathies. Br Med J (Clin 1998;65:258-9. 47. Kazakov VM, Bogorodinsky DK, Res Ed) 1983;287:705-8. 34. Uemura M, Kosaka T, Shimohata T, et Znoyko ZV, Skorometz AA. The facio- 61. Askmark H, Olsson Y, Rossitti S. al. Dropped head syndrome in amy- scapulo-limb (or the facioscapulo- Treatable dropped head syndrome in otrophic lateral sclerosis. Amyotroph humeral) type of muscular dystrophy. hypothyroidism. Neurology Lateral Scler Frontotemporal Degener Clinical and genetic study of 200 cases. 2000;55:896-7. 2013;14:232-3. Eur Neurol 1974;11:236-60. 62. Furutani R, Ishihara K, Miyazawa Y, et 35. Sih M, Soliven B, Mathenia N, et al. 48. Barbagallo G, Arabia G, Valentino P, et al. [A case of hypothyroidism display- Head-drop: A frequent feature of late- al. Anti-GAD-associated inflammatory ing “dropped head” syndrome]. Rinsho onset myasthenia gravis. Muscle Nerve myopathy presenting with dropped head Shinkeigaku 2007;47:32-6. 2017;56:441-4. syndrome. Neurol Sci 2015;36:1517-9. 63. Bleck TP. Dropped head syndrome. 36. Rodolico C, Messina S, Toscano A, et 49. Lomen-Hoerth C, Simmons ML, Neurology 1993;43:846; author reply al. Axial myopathy in myasthenia: a Dearmond SJ, Layzer RB. Adult-onset 846-847. misleading cause of dropped head. nemaline myopathy: Another cause of 64. Yoshida S, Takayama Y. Licorice- Muscle Nerve 2004;29:329-30. dropped head. Muscle Nerve induced hypokalemia as a treatable 37. Swash M. Dropped-head and bent-spine 1999;22:1146-50. cause of dropped head syndrome. Clin syndromes; axial myopathies? Lancet 50. Hanisch F, Schneider I, Muller T, et al. onlyNeurol Neurosurg 2003;105:286-7. 1998;352:758. [Treatability of sporadic late onset 65. Taniguchi K, Okino I, Yamamoto N, et 38. Schranz C, Meinck HM. [Primary neu- nemaline myopathy]. Nervenarzt al. [Two cases with dropped head syn- rogenic and myogenic disorders of pos- 2013;84:955-61. drome caused by hypokalemic myopa- ture]. Orthopade 2004;33:583-90. 51. Mizuno Y, Mori-Yoshimura M, thy]. Rinsho Shinkeigaku 2011;51:110- 39. Racz A, Giede-Jeppe A, Schramm A, et Okamoto T, et al. Two cases of usesporadic 3. al. Lambert-Eaton myasthenic syn- late onset nemaline myopathy effective- 66. Beekman R, Tijssen CC, Visser LH, drome presenting with a “dropped head ly treated with immunotherapy. Rinsho Schellens RL. Dropped head as the pre- syndrome” and associated with antibod- Shinkeigaku 2016;56:605-11. senting symptom of primary hyper- ies against N-type calcium channels. 52. Chuquilin M, Al-Lozi M. Primary amy- parathyroidism. J Neurol 2002;249: Neurol Sci 2013;34:1253-4. loidosis presenting as “dropped head 1738-9. 40. Haegele-Link S, Bohl J, Karajanev P, syndrome”. Muscle Nerve 67. Rymanowski JV, Twydell PT. Treatable Urban PP. Chronic inflammatory 2011;43:905-9. dropped head syndrome in hyper- demyelinating polyradiculoneuropathy 53. Laurent C, Aouizerate J, Hourdille A, et parathyroidism. Muscle Nerve. (CIDP) as rare differential diagnosis of al. Dropped head syndrome with proxi- 2009;39:409-10. a dropped head syndrome. Klin mal myopathy revealing AL amyloido- 68. Ota K, Koseki S, Ikegami K, et al. Neurophysiol 2006;37:A76. sis. Joint Bone Spine 2018;85:779-81. [Dropped head syndrome as first mani- 41. de Oliveira CM, Fussiger H, Winckler 54. Rahim F, Gupta D, Bertorini TE, festation of primary hyperparathyroid PB, Saute JAM. Dropped head syn- Ledoux MS. Dropped head presentation myopathy]. Rinsho Shinkeigaku drome as a manifestation of Charcot- of mitochondrial myopathy. J Clin 2018;58:193-7. Marie-Tooth disease type 4C. Neuromuscul Dis 2003;5:108-14. 69. Astudillo L, Hollington L, Game X, et Neuromuscul Disord. 2018.Non-commercial55. Finsterer J. Dropped head syndrome in al. Cervical dystonia mimicking 42. Finsterer J, Frank M, Krexner E. mitochondriopathy. Eur Spine J dropped-head syndrome after radiother- Steroid-responsive dropped-head-syn- 2004;13:652-6. apy for laryngeal carcinoma. Clin drome due to polymyositis. Joint Bone 56. Rose MR, Levin KH, Griggs RC. The Neurol Neurosurg 2003;106:41-3. Spine 2010;77:485-6. dropped head plus syndrome: quantita- 70. Rowin J, Cheng G, Lewis SL, 43. Muppidi S, Saperstein DS, Shaibani A, tion of response to . Meriggioli MN. Late appearance of et al. Isolated neck extensor myopathy: Muscle Nerve 1999;22:115-8. dropped head syndrome after radiother- is it responsive to immunotherapy? J 57. Karpati G, Carpenter S, Engel AG, et al. apy for Hodgkin’s disease. Muscle Clin Neuromuscul Dis 2010;12:26-9. The syndrome of systemic carnitine Nerve 2006;34:666-9. 44. Mirchandani A, Chen AS. Isolated Neck deficiency. Clinical, morphologic, bio- 71. Appels C, Goekoop R. Dropped-head Extensor Myopathy: A Case chemical, and pathophysiologic fea- syndrome due to high-dose irradiation. Presentation of Rapid Onset and tures. Neurology 1975;25:16-24. J Rheumatol 2009;36:2316. Spontaneous Recovery. PM R 58. Liao JP, Waclawik AJ, Lotz BP, e al. 72. Abdul-Latif AA. Dropped shoulder syn- 2018;10:552-4. Myopathic dropped head syndrome: an drome: a cause of lower cervical radicu- 45. Larsen H, Bogaard PW, Oppel L. A case expanding clinicopathological spec- lopathy. J Clin Neurol 2011;7:85-9.

[Neurology International 2019; 11:8198] [page 57]