Combined Invasive Peripheral Nerve Stimulation in the Management of Chronic Post-Intracranial Disorder Headache: A Case Report

Round 1

Reviewer 1 Report (Previous Reviewer 2)

Overall all comments has been satisfactorily addressed. 

 

Author Response

Dear reviewer,

many thanks for your time, consideration and the overall fruitful interaction.

Reviewer 2 Report (New Reviewer)

The paper by Alexoudi et al deals with the used on supraorbital and occipital nerve stimulation in the management of secondary headache. The case is interesting and clearly written and address a very interesting topic. I have some doubts I would like to clarify with the help of the authors.

When the diagnosis of hydrocephalus was made, the patient was monitored with a device. This is a part of another study. I would like to understand with different with standard care it entailed. Moreover a timeline would be useful, since it is not clear how long the patient remained from the first VPS implement and  report to the stimulator implant. In addition, antimigraine dosages should be mentioned with the time they were used.

As another point, I do not follow the reasoning about the diagnosis of the headache. This seems a secondary headache, at least how it is presented. If a primary form contribution was suspected, I think that either botulinum or CGRP should have been tried (even referring the patient to another center) before considering the stimulator. I would not consider in fact the exploding headache as a valid reason to devoid patients of botulinum toxin since PREEMPT studies didn’t consider headache features. In conclusion I would

Table 1 does not contain the mediation number neither before nor after the treatment with the stimulator

Author Response

Dear reviewer,

thank you for your time, consideration and the fruitful interaction. Here is the reply to your comments:

The intracranial pressure Telemetry monitoring protocol, which was held between September 2016 and December 2019 provided us further information. It is considered a safe method if it is used for a limited period. Insertion of a telemetric device is not generally recommended for all patients with NPH, benign intracranial Hypertension, shunt or aqueduct stenosis. Most of the times in standard care our approach is based on clinical and imaging information.

The timeline of events is demonstrated in figure 2.

“Pharmacological treatment of her headaches with topiramate (100 mg twice daily, for 3 months), propranolol (120mg/daily, for 3 months), venlafaxine (150 mg daily, for 6 months, in combination with flunarizine), flunarizine (10 mg daily, for 2 months, in combination with flunarizine) proved to be ineffective.”

Yes, you are right. Exploding headache was not examined as a marker either in PREEMPT or other studies. Nevertheless, most of these studies had some limitations (e.g., blindness, which was resolved by the study of Pijpers JA in 2019).

However, I found interesting and useful in clinical praxis the finding that 92% of non-responders describes a build-up of pressure inside their head or an exploding headache. (Moshe Jakubowski, Peter J McAllister, Zahid H Bajwa, Thomas N Ward, Patty Smith, Rami Burstein. Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A. Pain. 2006 Dec 5;125(3):286-295).

“Most responders to botulinum toxin describe their head to be crushed, clamped, or stubbed by external forces, what we understand as imploding headache. We did not consider botulinum toxin injection, because the described exploding headache does not respond to this treatment [10,11]. Anti-CGRP monoclonal antibodies were not in our routine clinical practice when we were handling this case [12].”

The rating scales were applied 3 months before and 3 months after the combined PNS application. However, I am not sure if my reply responds to your question.

 

Reviewer 3 Report (New Reviewer)

 

In line 62 you state there was no history of headache in your patient who was suffering headache - do you mean previous history?

The character of the later headache in your patient reads like migraine, and would be consistent with `chronic migraine’. It has also followed post-operative wound infection and various surgical and other procedures, as well as the intracranial abnormailities. Why select the latter in categorising the headache? Why not, for instance, post-scalp incision chronic migraine? The relation is based only on time, not cause, unless you have more evidence. Could the headache at her time of first presentation also have been chronic migraine? The paper's title suggests to me an unfamilier headache entity, though your Discussion makes your interpretation clearer. 

Author Response

Dear reviewer,

thank you for your time, consideration and the fruitful interaction. Here is the reply to your comments:

Exactly. After your suggestion it has changed to: “There was no previous headache history…”

“The headache was long lasting, holocephalic, pulsating, exploding headache aggravated by routine physical activity, accompanied by photophobia, phonophobia, and nausea, not responding to common pain medication, influencing her daily activities and the quality of sleep.”

“The underlying organicity was excluded because, the headache was not related to pressure, and there were no other features and tests suggestive of valve malfunction or over- drainage. Therefore, our patient met the description of a severe non-aura chronic migraine [6].”

“…this new headache was daily, occurring for more than three months, and had the features of migraine headache, fulfilling the diagnostic criteria of chronic migraine [6].”

Thank you for elucidating the case. post-scalp incision chronic migraine in other words, persistent headache attributable to craniotomy cannot be excluded.

“….and is therefore considered either a secondary headache attributable to a nonvascular intracranial disorder or a persistent headache attributable to craniotomy to craniotomy (or in other words post-scalp incision chronic headache) [6,7]. A headache attributed to craniotomy, may be more diffuse and resemble tension type headache or migraine [6].”

Actually, the diagnosis of chronic migraine is based on time and duration of symptoms (Description: Headache occurring on 15 or more days/ month for more than three months, which, on at least eight days/month, has the features of migraine headache).

The initial headache when she first presented “exacerbated by lying down, and relieved by sitting up or standing” and therefore it does not resemble migraine.

 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Authors reported on a unique case of peripheral nerve stimulation in a patient suffering from migraine-typeheadaches after shunting for a hydrocephalus.
The 30 y.o. female patient was diagnosed as having a nor-commuricating hydrocephalus en then aventriculo-peritoneal device was placed into right ventricule. Some time after this procedure, she begun withheadaches resembling migratne-type headache. Common, frst-ine antimigraine drugs were adminusteredwithout effect.The patient (as authors described) became "refractory" to common ant-migraine drugs; then, aPNS system was placed, first in occipital nerves, and afterwards in the tempopro-parietal nerves.
Clinically, she improved, and patient-reported outcomes decreased in pain evaluation and improved in QOlones.
There are two main considerations.

Why the patient was not treated in the meanwhile with peripheral nerve block (occipitalisauiculotemporalis?Why botulinum toxin was not used?
Protocols for headache treatment may change among centers, but there is a mirimum consensus for treatingchronic headache (especially migraine) in which after 2 oral drug failures, botulinum toxin using PREEMPI protocol must be used in at least 2 sessions. Furthermore; occipital (and AT) nerve blocks could also improve tosuch patients. Evermore; for considering refractory, today, the failure to anti-CGRp monoclonal antibodies isrequired. The final step might be the peripheral nerve stimulation, never the second step before botulinumtoxin.
Nerve stimulation systems are quite expensive.
I finally consider that this procedure was not really indicated in this patient.

Author Response

Reviewer 1

Why the patient was not treated in the meanwhile with peripheral nerve block (occipitalisauiculotemporalis?Why botulinum toxin was not used?
Protocols for headache treatment may change among centers, but there is a mirimum consensus for treatingchronic headache (especially migraine) in which after 2 oral drug failures, botulinum toxin using PREEMPI protocol must be used in at least 2 sessions. Furthermore; occipital (and AT) nerve blocks could also improve tosuch patients. Evermore; for considering refractory, today, the failure to anti-CGRp monoclonal antibodies isrequired. The final step might be the peripheral nerve stimulation, never the second step before botulinumtoxin.
Nerve stimulation systems are quite expensive.
I finally consider that this procedure was not really indicated in this patient.

 

Dear reviewer,

Many thanks for your meaningful comments and your consideration.

We did not consider botulinum toxin injection, because the described exploding headache does not respond to this treatment. Anti-CGRP monoclonal antibodies were not in our routine clinical practice when we were handling this case. (lines 141-144).

There is no doubt that nerve stimulation systems are quite expensive. However, frequently such conditions create exhaustion for the patients themselves, but also for the health system, as they are forced to undergo repeated diagnostic tests and inadequate treatments. (lines 218-221).

 I totally agree that occipital nerve blocks could also offer a relief, however, our clinic has not experience with this technique.

Hopefully, we have successfully replied to your comments.

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments to case report

1. An interesting case to discuss. However some points to improve:

2. Author mentioned ‘Some authors suggested that the concept of shunt migraine should not be overlooked [2]’. - The reference provided was old 1997- based on a paediatric paper. No correlation to possible current ICHD 3 diagnosis were made.

3. The temporal relation between the hydrocephalus, shunt and headache was not clear. Did the patient has headache prior to the index event? suggest to do a timeline for clarity,

4. The neuroanatomy of pain/headache should be discussed and how this PNS’s addressed the pathophysiology should be discussed.

5. The headache history was too brief, all clinical information as per ICHD 3 is required.

6. The instruments used were not validated for secondary headaches for e.g MIDAS.  Please justify all the instruments used.

7. Neuroimaging of the shunt should be included.

8. Surface anatomy diagram of the electrodes placement should be included.

Author Response

x

Comments to case report. An interesting case to discuss. However some points to improve:

Dear reviewer,

Many thanks for your meaningful comments and your consideration. Hopefully, the revised manuscript is much improved.

 

1. Author mentioned ‘Some authors suggested that the concept of shunt migraine should not be overlooked [2]’. - The reference provided was old 1997- based on a paediatric paper. No correlation to possible current ICHD 3 diagnosis were made.

 

The text has been modified as follows; “It was identified that patients with treated idiopathic intracranial hypertension (IIH) had headaches that can be classifiable by current IHS criteria compatible with episodic and chronic tension- type headache, migraine with and without aura, analgesic overuse headache, idiopathic stabbing headache, and benign exertional headache”. (lines 83-86).

We also added the following citations:

• Friedman, D.I; Rausch, E.A. Headache diagnoses in patients with treated idiopathic intracranial hypertension. Neurology. 2002, 58,1551-1553.
• Larsson, J., Israelsson, H.; Eklund, A.; Malm, J. Epilepsy, headache, and abdominal pain after shunt surgery for idiopathic normal pressure hydrocephalus: the INPH-CRasH study. J Neurosurg. 2018, 128, 1674-1683.

 

 

 

1. The temporal relation between the hydrocephalus, shunt and headache was not clear. Did the patient has headache prior to the index event? suggest to do a timeline for clarity

 

You are right. The temporal relation was not clear. Therefore, we added Figure 2.

 

1. The neuroanatomy of pain/headache should be discussed and how this PNS’s addressed the pathophysiology should be discussed.

 

“The convergence of cervical, somatic and dural afferents on second-order nociceptors in the trigeminocervical complex (TCC) in animal studies provided the theoretical background for application of ONS. This indeed explains how the stimulation of the anatomically distant occiput relieves symptoms in patients with certain intractable headaches and a fronto-temporal pain distribution. Nevertheless, not all the patients experience adequate relief, and this is our case. In these conditions, the stimulation of supraorbital area produces a concordant paraesthesia, covering the painful frontal region with the stimulator-induced paraesthesia. This rationale explains the additional beneficial effect on holocephalic headaches offered by combined PNS.” (lines 194-202).

 

 

1. The headache history was too brief, all clinical information as per ICHD 3 is required.

 

“The headache was long lasting, holocephalic, pulsating, exploding headache aggravated by routine physical activity, accompanied by photophobia, phonophobia, and nausea, not responding to common pain medication, influencing her daily activities and the quality of sleep. The underlying organicity was excluded because, the headache was not related to pressure, and there were no other features and tests suggestive of valve malfunction or overdrainage. Therefore, our patient met the description of a severe non-aura chronic migraine.” (lines 123-129)

 

1. The instruments used were not validated for secondary headaches for e.g MIDAS.  Please justify all the instruments used.

“To assess headache severity, disability due to headache, quality of life, insomnia, depression, and anxiety before and after implantation we used the following rating scales: Visual Analog Scale Score (VAS), Migraine Disability Assessment Scale (MIDAS), Short Form (36) Health Survey (SF-36), Athens Insomnia Scale (AIS), Beck Depression Inventory (BDI II), Beck Anxiety Inventory (BAI). The MIDAS has not been validated for secondary headaches. However, we decided to include the above rating scale in our instruments because the described headache met the diagnostic criteria for chronic migraine.” (lines 155-161).

 

1. Neuroimaging of the shunt should be included.

To clarify the valve application, we added an arrow in Figure 4 which indicates the shunt.

 

1. Surface anatomy diagram of the electrodes placement should be included.

Figure 3 demonstrates a surface anatomy of the electrodes’ placement.

 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Description of the patient's headache and clinical evidence that supported the diagnosis of Chronic Migraine and failed treatment, warranting treatment by implantable occipital nerve stimulation would have been helpful. It might be helpful in defining the case-report's value further.

Treatment with implantatable occipital nerve stimulation was decided on the basis of a diagnosis of probable Chronic Intractable Migraine. The VP shunt and its revision, simply becomes a distraction, not the basis of treatment.

Perhaps a better description of the basis for diagnosis of  Chronic Intractable Migraine would be more informative, and provide justification for the treatment which proved effective.

Author Response

x

Dear reviewer,

Many thanks for your meaningful comments and your consideration. Hopefully, the revised manuscript is much improved.

Description of the patient's headache and clinical evidence that supported the diagnosis of Chronic Migraine and failed treatment, warranting treatment by implantable occipital nerve stimulation would have been helpful. It might be helpful in defining the case-report's value further.

We supported the headache description as follows: “The headache was long lasting, holocephalic, pulsating, exploding headache aggravated by routine physical activity, accompanied by photophobia, phonophobia, and nausea, not responding to common pain medication, influencing her daily activities and the quality of sleep. The underlying organicity was excluded because, the headache was not related to pressure, and there were no other features and tests suggestive of valve malfunction or overdrainage. Therefore, our patient met the description of a severe non-aura chronic migraine.” (lines 123-129).

 

Hopefully, we supported the case report’s value adding the following paragraph: “Neurosurgeons are not always familiar handling chronic, refractory, secondary to shunt placement headaches which are not related to the valve dysfunction. This condition creates exhaustion for the patients themselves, but also for the health system, as they are forced to undergo repeated diagnostic tests and inadequate treatments. These different kinds of headaches (e.g. migraines with or without aura, tension type headache) usually appear several times a month and tend to become chronic and drug resistant. As known chronic pain conditions are strictly linked with central sensitization. PNS modifies synaptic plasticity leading to clinically significant and sustained results. Therefore, we have the conviction that PNS could be considered as a possible solution in this population who have failed to respond to first line interventions.” (lines 218-227).

 

Treatment with implantatable occipital nerve stimulation was decided on the basis of a diagnosis of probable Chronic Intractable Migraine. The VP shunt and its revision, simply becomes a distraction, not the basis of treatment.

You are right. The VP shunt and its revision is not the basis of treatment. To clarify the temporal relation of the events we added Figure 2.

Perhaps a better description of the basis for diagnosis of Chronic Intractable Migraine would be more informative, and provide justification for the treatment which proved effective.

Based on the “Refractory chronic migraine consensus statement” we modified the text: “non-steroid anti-inflammatory drugs (NSAIDs) failed to control the headaches and the response to tramadol was transient. Pharmacological treatment of her headaches with topiramate, flunarazine, propranolol, venlafaxine proved to be ineffective. The headache did not subside or improve markedly after 3 classes of migraine prophylactic medications, each used for at least 3 months and such that was classified as refractory” [Martelletti, P.; Katsarava, Z.; Lampl, C.; Magis, D.; Bendtsen, L.; Negro, A., Russell, M.B; Mitsikostas, D-D.D.; Jensen, R.H. Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain. 2014, 15, 47]. (lines 137-141).

Author Response File: Author Response.pdf

Reviewer 4 Report

English should be checked by native English spearker.

Case description is not enough.

This single case report did not add any significant scientific finding.

Author Response

English should be checked by native English speaker.

Case description is not enough.

This single case report did not add any significant scientific finding.

Dear reviewer,

Many thanks for your meaningful comments and your consideration. Hopefully, the revised manuscript is much improved.

We supported the description of the case, and the headache description as follows:

 

“Neurological examination revealed no objective deficits. There was no headache history or medication overuse, and no family history of neurologic disorders. The findings of the general medical examination were normal.” (lines 100-102).

“The headache was long lasting, holocephalic, pulsating, exploding headache aggravated by routine physical activity, accompanied by photophobia, phonophobia, and nausea, not responding to common pain medication, influencing her daily activities and the quality of sleep. The underlying organicity was excluded because, the headache was not related to pressure, and there were no other features and tests suggestive of valve malfunction or overdrainage. Therefore, our patient met the description of a severe non-aura chronic migraine.” (lines 123-129).

 

Hopefully, we supported the case report’s value adding the following paragraph:

“Neurosurgeons are not always familiar handling chronic, refractory, secondary to shunt placement headaches which are not related to the valve dysfunction. This condition frequently creates exhaustion for the patients themselves, but also for the health system, as they are forced to undergo repeated diagnostic tests and inadequate treatments. These different kinds of headaches (e.g. migraines with or without aura, tension type headache) usually appear several times a month and tend to become chronic and drug resistant. As known chronic pain conditions are strictly linked with central sensitization. PNS modifies synaptic plasticity leading to clinically significant and sustained results. Therefore, we have the conviction that PNS could be considered as a possible solution in this population who have failed to respond to first line interventions.” (lines 218-227).

 

 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Thanks for your corrections. The manuscript can be accepted after minor text editing corrections.

Author Response

Dear reviewer,

Many thanks for your kind comments and your consideration. Hopefully, the manuscript has been successfully edited. 

Reviewer 4 Report

Bilateral parietal stimulation is not peripheral nerve stimulation.

The case description is not enough. Other causes of headaches were not excluded enough. 

Author Response

Dear reviewer,

Many thanks for your meaningful comments and your consideration. Hopefully, the revised manuscript is improved.

Bilateral parietal stimulation is not peripheral nerve stimulation.

Simultaneous stimulation of the occipital (ONS) and supraorbital nerves (SNS) is considered “Combined Peripheral Neurostimulation” and has been developed by Reed. Our technique is a variation of Reed’s method, and as such it could be characterized as “Combined Peripheral Neurostimulation”.

 

The case description is not enough. 

Some meaningful missing information was added in the case description.

“Her neurological exam was unrevealing except for bilateral papilledema.”

(line 100).

Other causes of headaches were not excluded enough. 

“Considering the findings of imaging and the intracranial pressure values, other cases of shunt-related headaches (e.g., intracranial hypotension, intermittent proximal obstruction, shunt failure without ventricular enlargement, increased ICP with a working shunt) were excluded [8].”

(lines 137-140)

The citations have been updated.